bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Cooling of High Power Density Electronics Using Sprays and Microjets
Authors: Fabbri Matteo , Jiang Shanjuan , Dhir Vijay K.
Published: February 2005

Direct cooling by means of jets and sprays has been considered as a solution to the problem of cooling of high power density electronic devices. Although both methods are capable of very high heat removal rates no criterion exists that helps one decide as to which one is preferable, when designing a cooling system for electronic applications. In this work, the results of an investigation of the performances of sprays and arrays of micro jets are reported. Experiments have been conducted using HAGO nozzles and orifice plates to create droplet sprays and arrays of micro jets, respectively. The liquid jets had diameters ranging from 69 to 250 μm and the pitches between the jets were 1, 2, and 3 mm. The test fluid was deionized water and the jet Reynolds number ranged between 43 and 3813. A comparison of heat transfer and pressure drop results obtained employing both sprays and jets has been carried out. The microjet arrays proved superior to the sprays since they required less pumping power per unit of power removed. A cooling module employing impinging jets was tested. Such a module would require three primary components: an orifice plate for forming jets or a nozzle to form the spray; a container to hold the nozzle, the heat source and the cooling liquid, which also serves as a heat exchanger to the ambient; and a pump which recirculates the coolant. A fan could be used to improve the heat transfer to the ambient, and it would allow the use of a smaller container. An impinging jets cooling module has been designed and tested. Heat fluxes as high as 300 W/cm2 at 80°C surface temperature could be removed using a system which includes a 4×6 array of microjets of water of 140 μm diameter impinging on a diode 5.0×8.7 mm2.
Traumatic work related mortality among seafarers employed in British merchant shipping, 1976–2002
Authors: Roberts S E , Marlow P B
Published: February 2005

Aims:To establish the causes and circumstances of all traumatic work related deaths among seafarers who were employed in British merchant shipping from 1976 to 2002, and to assess whether seafaring is still a hazardous occupation as well as a high risk occupation for suicide.

Methods:A longitudinal study of occupational mortality, based on official mortality files, with a population of 1 136 427 seafarer-years at risk.

Results:Of 835 traumatic work related deaths, 564 were caused by accidents, 55 by suicide, 17 by homicide, and 14 by drug or alcohol poisoning. The circumstances in which the other 185 deaths occurred, including 178 seafarers who disappeared at sea or were found drowned, were undetermined. The mortality rate for 530 fatal accidents that occurred at the workplace from 1976 to 2002, 46.6 per 100 000 seafarer-years, was 27.8 times higher than in the general workforce in Great Britain during the same time period. The fatal accident rate declined sharply since the 1970s, but the relative risk of a fatal accident was 16.0 in 1996–2002. There was no reduction in the suicide rate, which was comparable to that in most high risk occupations in Britain, from 1976 to 1995; but a decline since 1995.

Conclusions:Although there was a large decline in the fatal accident rate in British shipping, compared to the general workforce, seafaring has remained a hazardous occupation. Further prevention should focus on improvements in safety awareness among seafarers and shipping companies, reductions in hazardous working practices, and improvements in care for seafarers at risk of suicide.
Pneumoconiosis after sericite inhalation
Authors: Algranti E , Handar A M , Dumortier P , Mendonça E M C , Rodrigues G L , Santos A M A , Mauad T , Dolhnikoff M , De Vuyst P , Saldiva P H N , Bussacos M A
Published: February 2005

Background:Between 1997 and 1999 three sericite plant workers in Paraná, Brazil, were diagnosed with pneumoconiosis.

Aims:To investigate and describe the radiological, clinical, and pathological changes in miners and millers exposed to sericite dust with mineralogical characteristics of inhaled dust.

Methods:The working premises were visited to examine the sericite processing and to classify the jobs according to make qualitative evaluation. Respirable dust was collected and the amount of crystalline silica and particle size distribution were measured. Forty four workers were examined by a standard questionnaire for respiratory symptoms, spirometry, and chestxray. Material from an open lung biopsy was reviewed for histopathological and mineralogical analysis, together with sericite samples from the work site to compare the mineral characteristics in lung lesions and work area.

Results:Respirable dust contained 4.5–10.0% crystalline silica. Particle size distribution showed a heavy burden of very fine particles (23–55%) with a mean diameter of <0.5 μm. Mean age of sericite miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In 52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or above, and 18.2% (8/44) had a reduced FEV1. There was a significant association between exposure indices andxray category. Histological studies of the lung biopsy showed lesions compatible with mixed dust fibrosis with no silicotic nodules.xRay diffraction analysis of the lung dust residue and the bulk samples collected from work area showed similar mineralogical characteristics. Muscovite and kaolinite were the major mineral particle inclusions in the lung.

Conclusion:Exposure to fine sericite particles is associated with the development of functional and radiological changes in workers inducing mixed dust lesions, which are distinct histologically from silicosis.
Municipal pleural cancer mortality in Spain
Authors: López-Abente G , Hernández-Barrera V , Pollán M , Aragonés N , Pérez-Gómez B
Published: February 2005

Background:Pleural cancer is a recognised indicator of exposure to asbestos and mesothelioma mortality.

Aims:To investigate the distribution of municipal mortality due to this tumour, using the autoregressive spatial model proposed by Besag, York, and Molliè.

Methods:It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain’s 8077 municipal areas. Maps were plotted depicting standardised mortality ratios, smoothed relative risk (RR) estimates, and the distribution of the posterior probability that RR >1.

Results:There was a higher risk of death due to pleural cancer in well defined towns and areas, many of which correspond to municipalities where asbestos using industries once existed for many years, the prime example being the municipal pattern registered for Barcelona Province. The quality of mortality data, the suitability of the model used, and the usefulness of municipal atlases for environmental surveillance are discussed.
CATEGORIFICATIONS OF THE COLORED JONES POLYNOMIAL
Authors: KHOVANOV MIKHAIL
Published: February 2005

The colored Jones polynomial of links has two natural normalizations: one in which the n-colored unknot evaluates to [n + 1], the quantum dimension of the (n + 1)-dimensional irreducible representation of quantum [Formula: see text], and the other in which it evaluates to 1. For each normalization we construct a bigraded cohomology theory of links with the colored Jones polynomial as the Euler characteristic.
CYTOKINESIS IN HIGHER PLANTS
Authors: Jürgens Gerd
Published: February 2005

Cytokinesis partitions the cytoplasm between two or more nuclei. In higher plants, cytokinesis is initiated by cytoskeleton-assisted targeted delivery of membrane vesicles to the plane of cell division, followed by local membrane fusion to generate tubulo-vesicular networks. This initial phase of cytokinesis is essentially the same in diverse modes of plant cytokinesis whereas the subsequent transformation of the tubulo-vesicular networks into the partitioning membrane may be different between systems. This review focuses on membrane and cytoskeleton dynamics in cell plate a transient membrane compartment that is formed by the fusion of cytokinetic vesicles and eventually matures into the plasma membranes and cross-wall between daughter cells formation and expansion during somatic cytokinesis.
Differential effects of 17β-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins
Authors: Rzewuska-Lech Ewa , Jayachandran Muthuvel , Fitzpatrick Lorraine A. , Miller Virginia M.
Published: February 2005

Several studies demonstrate an association between osteoporosis and arterial calcific disease, both of which being common in elderly women. Estradiol and raloxifene, a selective estrogen receptor modulator, prevent bone loss in postmenopausal women. Little is known regarding how these agents affect arterial calcification. The aim of this study was to determine whether or not 17β-estradiol and raloxifene reduced vascular smooth muscle cell (VSMC) differentiation and expression of bone-associated proteins during phosphate-induced calcification in vitro. Aortic VSMC were cultured from adult, gonadally intact, and ovariectomized (OVX) female pigs. Calcifying medium was added, and cells were treated with solvent (control), 17β-estradiol (E2), or raloxifene. Extent of calcification and phenotypic expression of bone-associated proteins [matrix gla protein (MGP), osteoprotegerin (OPG), and bone sialoprotein (BSP)] were examined at 3-day intervals over 2 wk. Calcium content increased in all groups but was greater in VSMC derived from intact compared with OVX animals. E2 reduced calcification and preserved a contractile phenotype. Expression of OPG significantly decreased with time; this decrease was significantly greater in VSMC derived from OVX compared with gonadally intact pigs. E2 and raloxifene preserved expression of OPG only in VSMC from intact pigs. Expression of MGP increased significantly with time and was not affected by E2 or raloxifene treatments. E2 treatment significantly inhibited synthesis of BSP in cells from both groups. In conclusion, E2 slows differentiation of VSMC induced by excess phosphate. Effectiveness of raloxifene to preserve expression of bone cell-associated proteins depends on the hormonal status of the tissue donor.
Influence of Elderly Executive Cognitive Function on Attention in the Lower Visual Field during Step Initiation
Authors: Di Fabio Richard P. , Zampieri Cris , Henke Jennifer , Olson Karen , Rickheim David , Russell Michelle
Published: February 2005

Background: There is a well-established relationship between poor executive cognitive abilities and elderly fall risk, but the precise mechanism underlying this relationship is unknown. Older persons frequently fall or trip on objects below eye level, and it was hypothesized that the pathological mechanism linking low executive function and fall risk is a selective impairment in the resolution of visual attention in the lower visual fields. Objective: To determine ifnormally sighted older persons living in the community with deficits in executive cognitive abilities have a reduced resolution of visual attention in the lower visual fields compared to elderly and younger subjects with high executive abilities. Methods: Eye and head angulations were monitored as subjects fixated on a point rear-projected at eye level at the end of a 3- meter walkway. Visual stimuli were briefly presented (<300 ms) in the peripheral visual field (with and without distractors) to directly cue the selection of the right or left foot to lead a step over a foam obstacle resting at the subject’s feet. No saccades were allowed until the stimulus was extinguished, at which time a down-saccade-step sequence moved the foot over the obstacle. The resolution of visual attention (tested with gratings) and the influence of target eccentricity in the upper and lower visual fields were evaluated. The primary outcome measures were step error and obstacle contact rate, saccade occurrence after extinguished stimulus and the log of cue-saccade latency (limb-independent reaction time). Results: All groups experienced greater stepping errors than expected by chance when stimuli were presented in the lower versus upper visual field and with increasing eccentricity. However, the obstacle contact rate was greater, cue-saccade latency was prolonged, and fewer down-saccades were generated in the elderly group with poor executive abilities compared to those with high executive function and younger subjects. Conclusions: Loss of visual attention in the lower visual fields was not unique to elderly subjects with poor executive function. However, slowed processing time and reduction in the frequency of down-saccades associated with a low level of executive function potentially account for the mechanism linking executive abilities and fall risk.
Prostate Needle Biopsy: 12 vs. 18 Cores – Is It Necessary?
Authors: Pepe Pietro , Aragona Francesco
Published: February 2005

Introduction: The aim of this study is to compare the histological results of a prostate needle biopsy scheme of 12 and 18 cores used in 372 consecutive patients submitted to an early stage diagnosis programme for prostate cancer (PCa). Materials and Methods: From February 2002 to July 2003 a transperineal TRUS-guided prostate needle biopsy was performed in 372 patients aged 40–73. Indications for biopsy were: suspected DRE, total PSA (PSAt) >10 ng/ml; PSAt equal to 4–10, 2.6–3.9, ≤2.5 ng/ml and PSA F/T <25%, <20% and <15%, respectively. In 256 patients, we performed 12 cores and in 116 cases 18 cores. Results: 159 (42.7%) patients were diagnosed with PCa, 138 (37%) with BPH, 58 (15.7%) with chronic prostatitis, 15 (4%) with a HGPIN, 2 (0.6%) with ASAP. In patients that underwent 12 and 18 cores the incidence of PCa was 39.8 and 49%; the incidence of PCa in patients with PSA ≤10 and >10 ng/ml submitted to 12 and 18 cores was 35 vs. 47% and 57.8 vs. 52%, respectively. The preponderance of clinical stage T1c was 50% (12 cores) vs. 72% (18 cores). The median bioptic Gleason score in both groups resulted 6.6 (12 cores) and 6 (18 cores). In 110 (12 bioptic cores) and in 30 (18 bioptic cores) patients that underwent a RRP, the pTNM proved a significant clinical neoplasm (Gleason score ≧6 and/or tumoral volume >0.5 cm3) in the first group in all cases, while in the second group in 28/30 (94%) cases. Conclusions: Extended schemes of prostate needle biopsy of 18 or more cores increases the PCa diagnosis in early stage and should be adopted for young patients with a PSA <10 ng/ml, negative DRE and in case of rebiopsies.
CA9 Expression as a Prognostic Factor in Renal Clear Cell Carcinoma
Authors: Soyupak Bülent , Erdoğan Şeyda , Ergin Melek , Seydaoğlu Gülsah , Kuzgunbay Barış , Tansuğ Zühtü
Published: February 2005

Introduction: We investigated whether CA9 protein could be used as a prognostic tumor marker as well as a diagnostic biomarker in renal clear cell carcinoma. Materials and Methods: Nephrectomy specimens from 92 patients were used in this study. 80 of these were renal cell carcinomas, 10 adenomas and 2 oncocytomas. Of the renal cell carcinomas, 67 were clear cell carcinomas. Immunohistochemical analysis using CA9 monoclonal antibody (M75) was performed on paraffin-embedded specimens. CA9 staining was correlated with tumor stage, grade, lymph node involvement, distant metastasis and cumulative survival time. Results: CA9 was present in 91.2% of clear cell carcinomas. Low staining was a poor prognostic factor, and conversely high staining a good prognostic one. CA9 expression was found to be the best prognostic factor when compared with T stage and grade. Even in low-grade and stage tumors, the presence of low expression correlated with lowered survival times. Conclusions: On the basis of our study, CA9 is a significant molecular marker in renal clear cell carcinomas. Decreased CA9 expression is independently associated with poor survival. CA9 can be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CA9 targeted therapies.
Prevention of Irinotecan-Induced Diarrhea by Oral Sodium Bicarbonate and Influence on Pharmacokinetics
Authors: Tamura Takao , Yasutake Koichi , Nishisaki Hogara , Nakashima Takatoshi , Horita Kazutugu , Hirohata Sigeya , Ishii Arata , Hamano Kenichi , Aoyama Nobuo , Shirasaka Daisuke , Kamigaki Takashi , Kasuga Masato
Published: February 2005

Alkalization of the intestinal tract by oral administration of sodium bicarbonate has been reported to be a promising method for preventing delayed diarrhea, a dose-limiting toxicity in patients receiving chemotherapy with irinotecan hydrochloride. However, it is feared that this method may adversely affect the pharmacokinetics of irinotecan by inhibiting its intestinal absorption and that of its active metabolites. We compared the pharmacokinetics and toxicity of irinotecan with and without oral alkalization in a cross-over study that enrolled 10 colorectal cancer patients. We found that alkalization did not decrease the blood levels of irinotecan and its active metabolite. In fact, the area under concentration versus time curves (AUCs) of irinotecan and 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) were statistically equivalent both with and without oral alkalization. Also, the AUC of SN-38 with alkalization was statistically equivalent or larger than that without alkalization. Oral alkalization reduced the incidence of diarrhea and gastrointestinal symptoms, and these adverse effects were not worsened by long-term administration. These results suggest that oral alkalization can control diarrhea and gastrointestinal toxicity without decreasing the blood levels of irinotecan and its active metabolites, thus improving the tolerability of long-term chemotherapy without reducing efficacy.
Increased Serum CA-15.3 Levels in Patients with Megaloblastic Anemia due to Vitamin B12 Deficiency
Authors: Symeonidis Argiris , Kouraklis-Symeonidis Alexandra , Apostolopoulos Dimitris , Arvanitopoulou Evangelia , Giannakoulas Nikolaos , Vassilakos Pavlos , Zoumbos Nicholas
Published: February 2005

Objectives: To estimate the usefulness of serum tumor markers’ monitoring, as predictors of gastric cancer in patients with pernicious anemia. Patients and Methods: We investigated serum levels of carcinoembryonic antigen (CEA), α-fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with pernicious anemia and in 24 healthy controls, matched for age and sex. In 38 patients, the evaluation was repeated 1–6 months after the correction of cobalamin deficiency. Results: All patients and controls had normal serum CEA and α-FP, and the levels of these markers as well as those of CA-125 and CA-19.9 did not differ between the two groups. All 50 patients, but only 2 controls exhibited increased serum CA-15.3, and the difference between the two groups was very significant (129.4 ± 84.9 vs. 19.8 ± 7.3 IU/ml, p < 0.001), while no difference between males and females was found. A thorough clinical examination of all patients, and mammographic study in 18 females did not reveal any finding suspicious of breast cancer. CA-15.3 levels were positively correlated with serum lactate dehydrogenase, and negatively with B12 and hemoglobin, but they were substantially decreased after the correction of anemia, in all 38 patients tested, and in 33 of them they were restored to normal. After a median follow-up of 34 months, one patient developed a colon cancer, but none showed any sign suspicious of breast cancer. Conclusions: Serum CA-15.3 shows an aberrant increase in untreated patients with pernicious anemia, which is reversed after the correction of the anemia. The possible origin seems unrelated to mammary tissue, and may be released by the apoptosing bone marrow megaloblastic erythroblasts.
Gemcitabine Combined with Oxaliplatin (GEMOX) as Second-Line Chemotherapy in Patients with Advanced Ovarian Cancer Refractory or Resistant to Platinum and Taxane
Authors: Raspagliesi Francesco , Zanaboni Flavia , Vecchione Francesca , Hanozet Francesco , Scollo Paolo , Ditto Antonino , Grijuela Barbara , Fontanelli Rosanna , Solima Eugenio , Spatti Gianbattista , Scibilia Giuseppe , Kusamura Shigeki
Published: February 2005

Objectives: The aimof this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer. Methods: Twenty patients received a 30–60-min infusion of gemcitabine a week for 2 weeks, followed by 120–180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m2, respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory. Results: Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9–51%). Conclusion: A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.
Divergent Patterns of Allelic Alterations in Premalignant Laryngeal Lesions Indicate Differences in the Impact of Morphological Grading Characteristics
Authors: Kleist Britta , Poetsch Micaela
Published: February 2005

Objectives: Classic histological grading and molecular genetic analysis of epithelial hyperplastic laryngeal lesions (EHLL) were correlated in an attempt to elucidate, which classic marker reflects best the gradual progression of laryngeal premalignant lesions as determined by an increasing number of molecular genetic aberrations. Methods: Thirty-two EHLL were grouped according to four grades of nuclear atypia, four degrees of epithelial maturation and three groups of overall and suprabasal mitotic activity. Overall and suprabasal proliferative activity were measured by MIB-1 immunostaining and staged according to four levels. Allelic imbalance was determined by PCR using 32 microsatellite loci at nine chromosomal arms. Results: Of the six classic criteria, only progressive mitotic indices correlated with allelic alterations in a remarkable variety of microsatellite markers, especially at chromosome 17p. Conclusion: Using the number of allelic alterations as standard for assessment, this preliminary study gives first evidence that certain morphological criteria could reflect differently the gradual progression of premalignant laryngeal lesions with mitotic index being the most promising marker. Further studies with long-term follow-up are required to prove the predictive value of these criteria in daily practice.
Comparison of Haplotype Inference Methods Using Genotypic Data from Unrelated Individuals
Authors: Xu Hongyan , Wu Xifeng , Spitz Margaret R. , Shete Sanjay
Published: February 2005

Objective: Haplotypes are gaining popularity in studies of human genetics because they contain more information than does a single gene locus. However, current high-throughput genotyping techniques cannot produce haplotype information. Several statistical methods have recently been proposed to infer haplotypes based on unphased genotypes at several loci. The accuracy, efficiency, and computational time of these methods have been under intense scrutiny. In this report, our aim was to evaluate haplotype inference methods for genotypic data from unrelated individuals. Methods: We compared the performance of three haplotype inference methods that are currently in use – HAPLOTYPER, hap, and PHASE – by applying them to a large data set from unrelated individuals with known haplotypes. We also applied these methods to coalescent-based simulation studies using both constant size and exponential growth models. The performance of these methods, along with that of the expectation-maximization algorithm, was further compared in the context of an association study. Results: While the algorithm implemented in the software PHASE was found to be the most accurate in both real and simulated data comparisons, all four methods produced good results in the association study.
Association in Multifactorial Traits: How to Deal with Rare Observations?
Authors: Jannot A.-S. , Essioux L. , Clerget-Darpoux F.
Published: February 2005

To detect the role of a candidate gene for a trait in a sample of individuals, we may test SNP haplotype or diplotype effects. For a limited sample size, many haplotype or diplotype categories may contain few individuals. This involves a power decrease when testing the association between the trait and the haplotypes or diplotypes as these categories provide little additional information while increasing the degrees of freedom. The present paper proposes a new strategy to group rare categories based on a measure of similarity between haplotypes or diplotypes and compares it to two other possible strategies to deal with rare categories: a SNP selection strategy based on haplotype diversity, and a grouping strategy that pools all rare categories into a single baseline group. This comparison is performed by means of simulation under four scenarios. We show that this new strategy shows the largest increase in power irrespective of the model underlying the candidate gene in the studied trait. This strategy therefore provides a powerful alternative to currently used methods to reduce the number of rare categories.
Genetic Determination of Acute Phase Reactant Levels: The Strong Heart Study
Authors: Best Lyle G. , North Kari E. , Tracy Russell P. , Lee Elisa T. , Howard Barbara V. , Palmieri Vittorio , MacCluer Jean W.
Published: February 2005

Objective: C-reactive protein (CRP), fibrinogen and plasminogen activating inhibitor-1 (PAI-1) are acute phase reactants (APRs); and high levels are indicative of physiologic inflammatory responses. Basal (non-stimulated) APR levels have also been shown to predict atherosclerotic complications in a number of populations. We sought to determine the relative contributions of genetic and environmental factors influencing basal serum levels of APRs. Methods: This study used univariate quantitative genetic analyses to partition the phenotypic variance of these APRs into their additive genetic and environmental components using maximum likelihood variance decomposition methods. Bivariate analyses were done to detect genetic correlation between APRs. The computer program SOLAR was used to perform these analyses. Results: The Strong Heart Study (SHS) includes information on approximately 1,294 American Indian relative pairs. The proportion of variance due to environmental and acquired covariates affecting these APRs was modest, ranging from 16–20%. The proportion of variance due to genetic factors (heritability) ranged from 24–46%. In addition, there were significant genetic correlations between CRP/fibrinogen (ρ = 0.41 ± 0.12) and CRP/PAI-1 (ρ = 0.46 ± 0.19); but not between fibrinogen/PAI-1. Conclusion: In the SHS cohort, the levels of APRs are determined to a substantial degree by genetic influences, and CRP shares common genetic determinants with fibrinogen and PAI-1.
Continuous Insulin Infusion in Hyperglycaemic Extremely-Low- Birth-Weight Neonates
Authors: Ng Sze May , May Judith E. , Emmerson Anthony J.B.
Published: February 2005

Background: The inability of the newborn to inhibit gluconeogenesis in response to a glucose infusion leading to insulin resistance has been postulated as an important cause of hyperglycaemia observed in premature infants. Aim: The aim of this study was to determine the efficiency and rate of response to continuous insulin infusion in improving glucose tolerance in hyperglycaemic extremely-low-birth-weight (ELBW) neonates (≤1,000 g) compared to neonates with birth weight >1,000 g (LBW). Methods: We included in the study 115 consecutive neonates in the neonatal intensive care unit who developed hyperglycaemia from January 2000 to December 2001. A standard protocol for the use of exogenous insulin infusions was commenced for all hyperglycaemic neonates. The efficiency of continuous insulin infusion was compared in two groups of infants: ELBW ≤1,000 g compared with neonates with birth weight >1,000 g (LBW). Results: The duration (hours) of insulin infusion required to normalise blood glucose level was significantly longer in the ELBW group compared to LBW group (p < 0.0001). Average insulin infusion (units/kg/h) required to maintain normoglycaemia was also significantly higher in the ELBW group (p < 0.0001). No significant difference was found in the mean amount of intravenous dextrose tolerated, mean postnatal age (hours) at which infusions were initiated and the average blood glucose recorded. ELBW infants were more likely to receive steroid administration, have surgery, higher CRIB scores and sepsis. Conclusion: Continuous insulin infusion was relatively safe and effective in the treatment of persistent hyperglycaemia in premature neonates. No serious adverse side effects of insulin therapy were noted. With the current protocol for use of exogenous insulin infusion at our unit, the response to treatment was significantly slower in the ELBW neonates. The dose of insulin infusion required to maintain normoglycaemia was also higher in this group of neonates. There may be a need for different treatment schedules for this subgroup of neonates so that normalisation of blood glucose can be achieved earlier.
Incomplete Stent Apposition After Implantation of Paclitaxel-Eluting Stents or Bare Metal Stents
Authors: Tanabe Kengo , Serruys Patrick W. , Degertekin Muzaffer , Grube Eberhard , Guagliumi Giulio , Urbaszek Wilhelm , Bonnier Johannes , Lablanche Jean-Michel , Siminiak Tomasz , Nordrehaug Jan , Figulla Hans , Drzewiecki Janusz , Banning Adrian , Hauptmann Karl , Dudek Dariusz , Bruining Nico , Hamers Ronald , Hoye Angela , Ligthart Jurgen M.R. , Disco Clemens , Koglin Jörg , Russell Mary E. , Colombo Antonio
Published: February 2005

Background—The clinical impact of late incomplete stent apposition (ISA) for drug-eluting stents is unknown. We sought to prospectively investigate the incidence and extent of ISA after the procedure and at 6-month follow-up of paclitaxel-eluting stents in comparison with bare metal stents (BMS) and survey the clinical significance of ISA over a period of 12 months.

Methods and Results—TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This intravascular ultrasound (IVUS) substudy included patients who underwent serial IVUS examination after the procedure and at 6 months (BMS, 240 patients; SR, 113; MR, 116). The qualitative and quantitative analyses of ISA were performed by an independent, blinded core laboratory. More than half of the instances of ISA observed after the procedure resolved at 6 months in all groups. No difference in the incidence of late-acquired ISA was observed among the 3 groups (BMS, 5.4%; SR, 8.0%; MR, 9.5%;P=0.306), with a similar ISA volume (BMS, 11.4 mm3; SR, 21.7 mm3; MR, 8.5 mm3;P=0.18). Late-acquired ISA was the result of an increase of vessel area without change in plaque behind the stent. Predictive factors of late-acquired ISA were lesion length, unstable angina, and absence of diabetes. No stent thrombosis occurred in the patients diagnosed with ISA over a period of 12 months.

Conclusions—The incidence and extent of late-acquired ISA are comparable in paclitaxel-eluting stents and BMS. ISA is a pure IVUS finding without clinical repercussions.
Amiodarone Improves Cardiac Sympathetic Nerve Function to Hold Norepinephrine in the Heart, Prevents Left Ventricular Remodeling, and Improves Cardiac Function in Rat Dilated Cardiomyopathy
Authors: Tachikawa Hitoshi , Kodama Makoto , Watanabe Kenichi , Takahashi Toshihiro , Ma Meilei , Kashimura Takeshi , Ito Masahiro , Hirono Satoru , Okura Yuji , Kato Kiminori , Hanawa Haruo , Aizawa Yoshifusa
Published: February 2005

Background—

It is unclear how amiodarone therapy exerts its effects on left ventricular remodeling and cardiac sympathetic nerve function in chronic heart failure. We investigated long-term effects of amiodarone on rat dilated cardiomyopathy after healing of cardiac myosin–induced autoimmune myocarditis.

Methods and Results—

Rats were treated with oral amiodarone or vehicle for 6 weeks. We determined cardiac function, left ventricular remodeling, and cardiac sympathetic nerve function with iodine-125–labeled metaiodobenzylguanidine ([I
125
]MIBG). Amiodarone treatment improved left ventricular pressure, central venous pressure, and rate of isovolumetric contraction and decreased ventricular weight (
P
<0.005). Expression of cytokine mRNA was unchanged; expression of atrial natriuretic peptide, collagen III, and transforming growth factor-β
1
mRNA was decreased in amiodarone-treated rats (
P
<0.05). Phenotype of myosin heavy chain was moved toward that of normal rats by amiodarone. Initial myocardial uptake of MIBG decreased by 67% (
P
<0.001) and washout rate accelerated by 221% in rats with chronic heart failure compared with normal rats. Whereas amiodarone decreased the initial uptake by 71% in normal rats, amiodarone decelerated the early washout and the late washout and improved the late myocardial distribution of MIBG in rats with chronic heart failure (257% compared with vehicle-treated rats with chronic heart failure;
P
<0.01). In proportion to MIBG distributions, cardiac tissue catecholamines were increased by amiodarone treatment.

Conclusions—

Long-term amiodarone treatment prevented left ventricular remodeling and improved cardiac function in rat dilated cardiomyopathy. Long-term amiodarone treatment also restored cardiac sympathetic tone to hold norepinephrine in the heart.
Distinct Heritable Patterns of Angiographic Coronary Artery Disease in Families With Myocardial Infarction
Authors: Fischer Marcus , Broeckel Ulrich , Holmer Stephan , Baessler Andrea , Hengstenberg Christian , Mayer Bjoern , Erdmann Jeanette , Klein Gernot , Riegger Guenter , Jacob Howard J. , Schunkert Heribert
Published: February 2005

Background—

Coronary artery disease (CAD) and myocardial infarction (MI) are significantly determined by genetic background. Whether distinct angiographic features of CAD are affected by inherited factors has never been investigated. Thus, we analyzed comprehensively the extent to which various aspects of CAD, including disease severity, distribution of lesions, presence of coronary calcification, morphology of stenoses, and anatomic characteristics, are under genetic control.

Methods and Results—

We retrospectively studied the coronary angiograms of 882 siblings with CAD from 401 families. These families were ascertained through index patients defined by MI before the age of 60 years and at least 1 sibling with MI or coronary revascularization procedures. Heritability calculations were performed with variance-component analysis. Additionally, recurrence risks to siblings were analyzed. Traditional cardiovascular risk factors and age at the first coronary event displayed significant heritable components. After adjustment for age and sex, significant heritabilities were identified for proximal stenoses, in particular, left main CAD (
h
2
=0.49±0.12;
P
=0.01), coronary calcification (
h
2
=0.51±0.17;
P
=0.001), and ectatic coronary lesions (
h
2
=0.52±0.07;
P
=0.001). In contrast, no heritability was found for distal disease (
h
2
=0.05±0.19; NS), the pattern of coronary arterial blood supply, or the number of diseased vessels. Calculation of recurrence risks in siblings largely confirmed the heritability estimates.

Conclusions—

Distinct morphological characteristics associated with CAD show different degrees of heritability. Notably, the most hazardous localizations, like left main or proximal disease, display a high heritability. In contrast, some features of coronary morphology, such as distal disease, do not appear to be markedly influenced by heritable factors.
Potent Inhibitory Effect of Sirolimus on Circulating Vascular Progenitor Cells
Authors: Fukuda Daiju , Sata Masataka , Tanaka Kimie , Nagai Ryozo
Published: February 2005

Background—

Neointimal hyperplasia is the major cause of in-stent restenosis (ISR). The sirolimus-eluting stent (SES) has emerged as a promising therapy to prevent ISR; however, the exact mechanism by which locally delivered sirolimus, an immunosuppressive agent, prevents ISR remains unknown. Recent evidence suggests that circulating progenitor cells may contribute to neointimal formation.

Methods and Results—

Mononuclear cells (MNCs) were isolated from peripheral blood of healthy human volunteers. Smooth muscle (SM)–like cells outgrew from the culture of MNCs (1×10
6
) in the presence of platelet-derived growth factor-BB and basic fibroblast growth factor, whereas endothelial cell–like cells were obtained in the presence of vascular endothelial growth factor. Sirolimus potently inhibited SM-like cell outgrowth. The number of SM-like cells was significantly reduced at a concentration as low as 0.1 ng/mL (15.9±5.8% of control,
P
<0.001). Sirolimus also exerted an inhibitory effect on endothelial cell–like cells that originated from MNCs. Wire-mediated vascular injury was induced in femoral arteries of bone marrow chimeric mice. Either vehicle or sirolimus was administered locally to the perivascular area of the injured arteries. Sirolimus significantly reduced neointima hyperplasia at 4 weeks (intima/media ratio 2.0±0.3 versus 1.0±0.2,
P
<0.05) with a decreased number of bone marrow–derived SM-like cells and hematopoietic cells in the lesion. Reendothelialization was retarded in the arteries treated with sirolimus.

Conclusions—

The potent inhibitory effects of sirolimus on circulating smooth muscle progenitor cells may mediate the clinical efficacy of SES, at least in part. Sirolimus potentially may affect reendothelialization after stent implantation.
Postischemic Gene Transfer of Interleukin-10 Protects Against Both Focal and Global Brain Ischemia
Authors: Ooboshi Hiroaki , Ibayashi Setsuro , Shichita Takashi , Kumai Yasuhiro , Takada Junichi , Ago Tetsuro , Arakawa Shuji , Sugimori Hiroshi , Kamouchi Masahiro , Kitazono Takanari , Iida Mitsuo
Published: February 2005

Background—

Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia.

Methods and Results—

Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or β-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1β, or tissue necrosis factor-α in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623±2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase–mediated dUTP-biotin in situ nick end labeling–positive cells were diminished by the IL-10 gene transfer with attenuated IL-1β and augmented tissue necrosis factor-α.

Conclusions—

Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.
T-Vector Direction Differentiates Postpacing From Ischemic T-Wave Inversion in Precordial Leads
Authors: Shvilkin Alexei , Ho Kalon K.L. , Rosen Michael R. , Josephson Mark E.
Published: February 2005

Background—

Postpacing precordial T-wave inversion (TWI), known as cardiac memory (CM), mimics ischemic precordial TWI, and there are no established ECG criteria that adequately distinguish between the two. On the basis of CM properties (postpacing sinus rhythm T vector approaching the direction of the paced QRS vector), we hypothesized that CM induced by right ventricular pacing would manifest a TWI pattern different from that of precordial ischemic TWI, thereby discriminating between the two.

Methods and Results—

T-wave axis, polarity, and amplitude on a 12-lead ECG during sinus rhythm were compared between CM and ischemic patients. The CM group incorporated 13 patients who were paced in DDD mode with short atrioventricular delay for 1 week after elective pacemaker implantation. The ischemic group consisted of 47 patients with precordial TWI identified among 228 consecutive patients undergoing percutaneous coronary intervention for an acute coronary syndrome. The combination of (1) positive T
aVL
, (2) positive or isoelectric T
I
, and (3) maximal precordial TWI>TWI
III
was 92% sensitive and 100% specific for CM, discriminating it from ischemic precordial TWI.

Conclusions—

CM induced by right ventricular pacing results in a distinctive T-vector pattern that allows discrimination from ischemic precordial T-wave inversions regardless of the coronary artery involved.
High Blood Pressure Reduction Reverses Angiotensin II Type 2 Receptor–Mediated Vasoconstriction Into Vasodilation in Spontaneously Hypertensive Rats
Authors: You Dong , Loufrani Laurent , Baron Celine , Levy Bernard I. , Widdop Robert E. , Henrion Daniel
Published: February 2005

Background—

We have previously shown that angiotensin II type 2 receptor (AT
2
R) stimulation causes endothelium-dependent vasodilation that does not desensitize after chronic angiotensin II type 1 receptor (AT
1
R) blockade, suggesting a role for AT
2
R in antihypertensive treatment.

Methods and Results—

We recorded mean arterial pressure (MAP) and investigated AT
2
R by Western blot analysis, immunohistochemistry, and function in isolated mesenteric resistance arteries (205 μm in diameter) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) receiving the following for 4 weeks in drinking water: placebo, AT
1
R blockade (candesartan; 2 mg/kg per day), ACE inhibitor (perindopril; 3 mg/kg per day), nonselective vasodilator (hydralazine; 16 or 24 mg/kg per day), or candesartan plus hydralazine (16 mg/kg per day). In precontracted isolated arteries, AT
2
R stimulation (angiotensin II in the presence of candesartan) caused vasodilation in WKY rats (MAP=118 mm Hg) and vasoconstriction in SHR (MAP=183 mm Hg). In SHR treated with candesartan (MAP=146 mm Hg) or hydralazine (16 mg/kg per day; MAP=145 mm Hg), AT
2
R-induced contraction was reduced by 50%. In SHR treated with perindopril (MAP=125 mm Hg), AT
2
R stimulation induced vasodilation. In SHR treated with hydralazine (24 mg/kg per day; MAP=105 mm Hg) and in SHR treated with hydralazine (16 mg/kg per day) plus candesartan (MAP=102 mm Hg), an AT
2
R-mediated vasodilation was restored. Immunochemistry and Western blot analysis showed that AT
2
R expression, lower in SHR than in WKY rats, was restored to normal levels by treatments reducing arterial pressure in SHR.

Conclusions—

Our results suggest that in resistance arteries of SHR, (1) AT
2
R is downregulated by hypertension, and (2) specific and nonspecific antihypertensive treatments restore AT
2
R expression and vasodilator functions.
Reduced Angiotensin II and Oxidative Stress Contribute to Impaired Vasodilation in Dahl Salt-Sensitive Rats on Low-Salt Diet
Authors: Drenjancevic-Peric Ines , Lombard Julian H.
Published: February 2005

This study investigated the role of impaired angiotensin II (Ang II) modulation in contributing to reduced vascular relaxation in isolated middle cerebral arteries (MCA) (100 to 200 μm in diameter) of normotensive Dahl salt-sensitive (SS) rats maintained on low salt (LS) diet (0.4% NaCl) for 9 to 10 weeks. MCA from SS rats on LS diet (n=6 to 9) constricted in response to reduction of perfusate and superfusate PO
2
to 35 to 40 mm Hg or acetylcholine (ACh). Vasodilator responses to reduced PO
2
and ACh were restored in SS.13
BN
consomic rats that are 98% genetically identical to SS rats, but exhibit normal regulation of their renin-angiotensin system (RAS). This restored dilation could be prevented by feeding SS.13
BN
rats high-salt (HS) diet (4% NaCl) for 3 days to suppress Ang II. A continuous intravenous infusion of a subpressor dose (3 ng/kg per minute) of Ang II for 3 days restored vasodilator responses to ACh and reduced PO
2
in SS.13
BN
rats on HS diet and in SS rats on LS diet. Superoxide scavenging with tempol (100 μmol/L) restored vasodilator responses to ACh and reduced PO
2
in MCA of SS rats on LS diet, but did not affect vasodilator responses in MCA of SS.13
BN
rats on LS diet. These data indicate that exposure to chronically low Ang II levels leads to impaired vascular relaxation in SS rats, even when the animals are on LS diet and normotensive. This impaired relaxation appears to be mediated by increased levels of oxidative stress in the arteries.
Brain Activation during Face Perception: Evidence of a Developmental Change
Authors: Aylward E. H. , Park J. E. , Field K. M. , Parsons A. C. , Richards T. L. , Cramer S. C. , Meltzoff A. N.
Published: February 2005

Behavioral studies suggest that children under age 10 process faces using a piecemeal strategy based on individual distinctive facial features, whereas older children use a configural strategy based on the spatial relations among the face's features. The purpose of this study was to determine whether activation of the fusiform gyrus, which is involved in face processing in adults, is greater during face processing in older children (12–14 years) than in younger children (8– 10 years). Functional MRI scans were obtained while children viewed faces and houses. A developmental change was observed: Older children, but not younger children, showed significantly more activation in bilateral fusiform gyri for faces than for houses. Activation in the fusiform gyrus correlated significantly with age and with a behavioral measure of configural face processing. Regions believed to be involved in processing basic facial features were activated in both younger and older children. Some evidence was also observed for greater activation for houses versus faces for the older children than for the younger children, suggesting that processing of these two stimulus types becomes more differentiated as children age. The current results provide biological insight into changes in visual processing of faces that occur with normal development.