bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Nondipper” Elderly: A Clinical Entity or a Bias?
Authors: Pasqualini Rita , Foroni Micaela , Salvioli Gianfranco , Mussi Chiara
Published: May 2004

Objectives: To determine the prevalence of nondipper (ND) blood pressure profile in the elderly and to ascertain whether the ND pattern of ambulatory blood pressure in the elderly is an artifact or represents a specific clinical entity.

Design: Cross‐sectional, observational study.

Setting: Cardiovascular diagnostic center, division of geriatrics, secondary care, institutional practice.

Participants: Sixty‐five consecutive community‐dwelling elderly hypertensive patients referred to the cardiovascular center.

Measurements: The patients underwent actigraphy and ambulatory blood pressure monitoring and completed a sleep assessment questionnaire. Patients were divided based on the night‐time decrease in blood pressure (>10%: “dippers” (n=19); <10%: “NDs” (n=46)).

Results: Nondippers displayed poorer quality of sleep, as demonstrated objectively by actigraphic data; they obtained a higher mean score±standard deviation on the sleep questionnaire (4.6±2.9 vs 3.0±1.1, P=.030) and were taking more benzodiazepines (33.1% vs 10.7%, P=.035), indicating that their usual sleep quality was worse than that of dippers. Multivariate analysis showed a strong correlation between nondipper profile and quality of sleep and also with comorbidity, total number of drugs being taken, and pulse pressure.

Conclusion: Actigraphy demonstrates impaired sleep in the nondipper elderly. Nevertheless, the nondipping pattern seems independent of the discomfort of cuff‐inflation during the night and occurs in association with higher comorbidity and polypharmacy; therefore, it cannot be considered a “bias,” but is related to detrimental clinical conditions that should be studied in depth.
Development and Validation of a Geriatric Knowledge Test for Medical Students
Authors: Lee Ming , Wilkerson LuAnn , Reuben David B. , Ferrell Bruce A.
Published: May 2004

Objectives: To assesses the reliability and validity of a geriatrics knowledge test designed for medical students.

Design: Cross‐sectional studies.

Setting: An academic medical center.

Participants: A total of 343 (86% of those sampled) medical students participated in the initial study, including 137 (76%) first‐year, 163 (96%) third‐year, and 43 (86% of those sampled) fourth‐year students in the 2000–2001 academic year. To cross‐validate the instrument, another 165 (92%) third‐year and 137 (76%) first‐year students participated in the study in the 2001–2002 academic year.

Measurements: An 18‐item geriatrics knowledge test was developed. The items were selected from a pool of 23 items. An established instrument assessing the clinical skills of medical students was included in the validation procedure.

Results: The instrument demonstrated good reliability (Cronbach α=0.80) and known‐groups and concurrent validity. Geriatrics knowledge scores increased progressively with the higher level of medical training (mean percentage correct=31.3, 65.3, and 66.5 for the first‐year, third‐year, and fourth‐year classes, respectively, P<.001). A significant (P<.01) relationship was found between the third‐year students' geriatrics knowledge and their clinical skills. Similar results, except the relationship between knowledge and clinical skills, were found in the cross‐validation study, supporting the reliability and known‐groups validity of the test.

Conclusion: The 18‐item geriatrics knowledge test demonstrated sound reliability and validity. The average scores of the student groups indicated substantial room for growth. The relationship between geriatrics knowledge and overall clinical skills needs further investigation.
HPA‐5b (Bra) neonatal alloimmune thrombocytopenia in Quebec: incidence and clinical outcome in 31 cases
Authors: Rousseau Julie , Goldman Mindy , David Michèle
Published: May 2004

BACKGROUND:  Clinical detection of neonatal allo‐immune thrombocytopenia (NAITP) is often less than the incidence predicted in prospective studies. The aims of this study were to calculate the observed and expected incidence of NAITP in Quebec, Canada, and to evaluate the clinical outcome of infants with anti‐HPA‐5b NAITP.

STUDY DESIGN AND METHODS:  Records from 1998 to 2002 of the only PLT serology laboratory for the province of Quebec were reviewed, as were hospital charts of all HPA‐5 cases. The number of expected NAITP cases was estimated with known alloantigen gene frequencies.

RESULTS:  Ninety cases of NAITP were identified. The clinical detection rate was 1 in 4100, with 9 to 30 percent of expected HPA‐1a and 11 to 23 percent of expected HPA‐5b NAITP cases detected. Seventy‐eight percent of cases of HPA‐5b NAITP were asymptomatic. Sixty‐three percent of all deliveries but 94 percent of HPA‐5b cases occurred in hospitals performing cord blood PLT counts.

CONCLUSION:  The NAITP detection rate was 25 to 50 percent of the rate reported in prospective trials. The less severe clinical presentation of NAITP owing to HPA‐5b was confirmed. The frequent routine determination of cord blood PLT counts may explain increased detection of asymptomatic NAITP involving anti‐HPA‐5b.
Window‐period human immunodeficiency virus transmission to two recipients by an adolescent blood donor
Authors: Phelps Ruby , Robbins Kenneth , Liberti Thomas , Machuca Ana , Leparc German , Chamberland Mary , Kalish Marcia , Hewlett Indira , Folks Thomas , Lee Lisa M. , McKenna Matthew
Published: May 2004

BACKGROUND:  Pooled NAT and donor screening have reduced the diagnostic window period for HIV in the blood donor population to approximately 10 to 15 days. This report describes two cases of transfusion‐acquired HIV infection and verification of transmission from the donor to the recipients, and attempts to identify how the 18‐year‐old donor acquired her infection.

STUDY DESIGN AND METHODS:  After a repeat donor had a positive HIV test result, two recipients of the donor's previous donation were identified and tested. The donor and recipients were interviewed and blood samples were obtained for HIV DNA sequencing and phylogenetic analysis.

RESULTS:  The two recipients had positive HIV test results. Phylogenetic analysis showed a high genetic similarity among the viruses (bootstrap 100%), consistent with transmission from the donor to the recipients. Four of five men with whom the donor had sexual contact during the critical time period when infection most likely occurred were located and tested; results were negative for HIV.

CONCLUSIONS:  Pooled NAT of blood donations has not eliminated the window period for HIV identification during seroconversion.
A new automated cell washer device for thawed cord blood units
Authors: Perotti Cesare G. , Fante Claudia Del , Viarengo Gianluca , Papa Pietro , Rocchi Loretta , Bergamaschi Paola , Bellotti Laura , Marchesi Andrea , Salvaneschi Laura
Published: May 2004

BACKGROUND:  The current available techniques to wash out DMSO from thawed umbilical cord blood (UCB) units are based essentially on standard centrifugation in an open system with various degrees of cell loss.

STUDY DESIGN AND METHODS:  We evaluated the capacity of a new automated closed device (Cytomate, Baxter, IL) to wash out the DMSO from thawed UCB units, saving at the same time the progenitor and accessory cells in terms of CD34+ cells and MNCs. We modified the standard software of the device and calculated the cell recovery on 25 UCB units. Moreover, we set up a new gas chromatographic method to exactly detect the DMSO removal rate.

RESULTS:  To evaluate the efficiency of the Cytomate device, we considered the postthawing (prewashing) versus postwashing cell recovery. The average recovery (%) in terms of total nucleated cells was 63.30 (range, 40.12‐89.00), CD34+ cells was 70.20 (range, 11.51‐89.01), CD3+ cells was 61.01 (range, 28.80‐87.08), CD4+ cells was 62.53 (range, 30.62‐96.73), CD8+ cells was 57.4 (range, 26.87‐94.72), CD19+ cells was 63.33 (range, 39.10‐90.33), CD16+/56+ cells was 70.67 (range, 8.91‐98.40), CFU‐GM was 74.33 (range, 20.23‐98.60), total CFUs was 82.34 (range, 14.83‐247.12), and viability was 89.67(range, 70.74‐98.30). The total working time required was, on average, 15 minutes (range, 7‐20).

CONCLUSIONS:  The Cytomate device demonstrated a satisfying efficiency in cell recovery and in maintaining the clonogenic power of the UCB graft. The removal rate of DMSO was practically complete with evident advantages for the recipient. Finally, the entire manipulation performed in a closed system revealed to be safe, maintaining the sterility of the graft.
Influence of hydration and mechanical characterization of carious primary dentine using an ultra‐micro indentation system (UMIS)
Authors: Angker Linny , Nijhof Niels , Swain Michael V. , Kilpatrick Nicola M.
Published: May 2004

The conditions under which mechanical properties of dentine are tested influence the values recorded. The aims of this study were to examine the effect of hydration on the mechanical properties of primary carious dentine and to provide information on changes in hardness and modulus of elasticity change caused by the demineralizing caries process in dentine. Three primary molar teeth with untreated carious dentine were prepared for nano‐indentation tests under both wet and dry conditions. Further tests were conducted on eight primary molars with untreated carious dentine under hydrated conditions. The mechanical properties of dehydrated carious dentine increased approximately 10‐fold for hardness and 100‐fold for the modulus of elasticity compared with hydrated dentine. The hardness and elastic modulus of the carious primary dentine deteriorated progressively toward the lesion cavity floor, ranging from 0.001 to 0.52 GPa and from 0.015 to 14.55 GPa, respectively, and could be fitted to a simple linear relationship when plotted in logarithmic scale vs. distance. The total depth of dentine affected was around 1100 µm parallel to the tubule direction. This depth was significantly greater than observed subjectively, implying that the demineralization process is more advanced than might be suspected on simple clinical examination.
Gene expression signatures in chronic and aggressive periodontitis: a pilot study
Authors: Papapanou Panos N. , Abron Armin , Verbitsky Miguel , Picolos Doros , Yang Jun , Qin Jie , Fine James B. , Pavlidis Paul
Published: May 2004

This pilot study examined gene expression signatures in pathological gingival tissues of subjects with chronic or aggressive periodontitis, and explored whether new subclasses of periodontitis can be identified based on gene expression profiles. A total of 14 patients, seven with chronic and seven with aggressive periodontitis, were examined with respect to clinical periodontal status, composition of subgingival bacterial plaque assessed by checkerboard hybridizations, and levels of serum IgG antibodies to periodontal bacteria assayed by checkerboard immunoblotting. In addition, at least two pathological pockets/patient were biopsied, processed for RNA extraction, amplification and labeling, and used to study gene expression using Affymetrix U‐133 A arrays. Based on a total of 35 microarrays, no significantly different gene expression profiles appeared to emerge between chronic and aggressive periodontitis. However, ade novogrouping of the 14 subjects into two fairly robust clusters was possible based on similarities in gene expression. These two groups had similar clinical periodontal status and subgingival bacterial profiles, but differed significantly with respect to serum IgG levels against the important periodontal pathogensPorphyromonas gingivalis, Tannerella forsythensisandCampylobacter rectus. These early data point to the usefulness of gene expression profiling techniques in the identification of subclasses of periodontitis with common pathobiology.
Color stability of resin matrix restorative materials as a function of the method of light activation
Authors: Janda Ralf , Roulet Jean‐François , Kaminsky Martin , Steffin Glenn , Latta Mark
Published: May 2004

The purpose was to investigate the influence of curing devices and curing times on the yellow value (b‐value) of composites, ormocers and compomers after performing a suntest (EN ISO 7491). Eight samples of Charisma (CH), Durafill (DU), Definite (DE), and Dyract AP (DY) each were light cured with Translux Energy (tungsten halogen light) for 20, 40 or 60 s and with Apollo 95‐E (plasma light) for 3, 10 or 20 s. All samples were subjected to a suntest. Before and after the suntest the yellow values (b‐values) were determined and the change (Δb) was calculated. When cured with Translux Energy for 20 and 40 s DU, CH, and DY revealed significantly negative Δb‐values. The b‐value of DE remained nearly constant. When cured for 60 s, DU and DE shifted to more yellow while CH and DY still bleached a little. When cured with Apollo 95‐E, a dramatic bleaching process of all materials investigated occurred after the suntest (significant negative Δb). It may be concluded that the bleaching of composites, ormocers and compomers depends on (i) the used light curing device and (ii) the chosen curing times. The tungsten halogen light provided highly significantly superior results.
Effect of acid etching time and technique on interfacial characteristics of the adhesive–dentin bond using differential staining
Authors: Wang Yong , Spencer Paulette
Published: May 2004

Dentin bonding using the total‐etch method has been claimed to be technique‐sensitive. The aim of this study is to examine the effect of acid‐etch variations on the dentin demineralization and interfacial structure of the adhesive–dentin bond using a differential staining technique. Single Bond adhesive with 35% phosphoric acid gel was used. The occlusal one‐third of the crown was removed from 60 extracted, unerupted human third molars. Smear layers were created by abrading the dentin with 600 grit SiC under water for 30 s. The prepared teeth were randomly assigned to four groups according to etching time (Group 1, 10 s; Group 2, 15 s; Group 3, 30 s; Group 4, 60 s). In each group, the etching gel was: (i) applied and spread to the dentin surface and left to stand undisturbed; (ii) applied and gently agitated during etching; (iii) applied without using dispensing tips for the syringe and left for the same period as above. After rinsing, the etched dentin was then treated with the adhesive per manufacturers' instructions. 3–5 µm thin sections of the adhesive/dentin (a/d) interface were cut with a microtome and stained with Goldner's trichrome. Stained, thin sections from each prepared tooth were imaged with light microscopy. The depth and extent of dentin demineralization, and the a/d interdiffusion zone were clearly visible by this differential staining microtechnique. The thickness of the interdiffusion zone increased as a function of etching time. However, the etchant gel application methods have a significant influence on dentin demineralization. Although agitating acid gel facilitates the penetration and etching into dentin, it should not be recommended, especially for longer etching time. These results indicated that the etching technique has a large effect on the profile of both dentin demineralization and interfacial structure.
Inhibitory effects of cacao bean husk extract on plaque formation in vitro and in vivo
Authors: Matsumoto Michiyo , Tsuji Masato , Okuda Jumpei , Sasaki Hidekazu , Nakano Kazuhiko , Osawa Kenji , Shimura Susumu , Ooshima Takashi
Published: May 2004

Cacao bean husk extract (CBH) has been shown to possess antibacterial and antiglucosyltransferase activities through its unsaturated fatty acids and epicatechin polymers, respectively. In the present study, the antiplaque activities of CBH were examined in vitro and in vivo. The extract inhibited the adherence of Streptococcus mutans MT8148 to saliva‐coated hydroxyapatite and reduced the accumulation of artificial dental plaque by S. mutans MT8148 on orthodontic wire. The number of mutans streptococci in dental plaque was also significantly reduced when human dental plaque was exposed to CBH from 21 children at 37°C for 1 h. For the in vivo study, 28 volunteers aged 19–29 yr old rinsed their mouth with CBH, before and after each intake of food and before sleeping at night for 4 d without using other oral hygiene procedures. Plaque depositions and the numbers of mutans streptococci were reduced in the subjects, compared with rinsing with 1% ethanol alone. These results indicate that CBH possesses significant antiplaque activity in vitro and in vivo.
Leached components from dental composites and their effects on fertility of female mice
Authors: Al‐Hiyasat Ahmad S. , Darmani Homa , Elbetieha Ahmed M.
Published: May 2004

This study investigated the effects of leached components from a resin‐based dental composite (Z‐100) and bisphenol A (BPA) on female mouse fertility. Leached components or BPA (5, 25 and 100 µg kg−1) were administered intragastrically daily to the test and distilled water to the control groups for 28 d. Female mice were then mated with sexually mature untreated males and their fertility was assessed. The results revealed a significant reduction in the number of pregnancies – 54.5% vs. 100% (control) – in mice treated with the leached components from the dental composite, which also showed an increase of 142% in relative ovary weights. Exposure to 25 and 100 µg kg−1 BPA resulted in significant increases in the total number of resorptions out of the total number of implantations and significant increases in relative uterine weights. Relative ovarian weights were significantly increased at the highest dose. High performance liquid chromatography analysis showed that tri‐(ethylene glycol)‐dimethacrylate (TEG‐DMA) was the major leached component (total: 5945 µg ml−1) from the composite, followed by bisphenol A glycerolate dimethacrylate (BIS‐GMA) (total: 2097 µg ml−1) and BPA (total: 78 µg ml−1). The results suggest that leached components from the dental composite used and commercially purchased BPA have adverse effects on the fertility and reproductive system of female mice.
Organ culture of the fetal mouse palate for screening the developmental toxicity of chemicals: A validation study
Authors: Kosazuma Tsuneo , Hashimoto Shiori , Ohno Hiromitsu , Chou Ming‐Jen , Shiota Kohei
Published: May 2004

ABSTRACT  Using in vitro organ culture of the fetal mouse palate in a chemically defined serumless medium, the toxicity of 24 chemical compounds was investigated. Explanted palates of day‐12.5 mouse fetuses were exposed for 72 h in vitro to various concentrations of each chemical, and the fusion rate and growth parameters were compared between the experimental group and respective controls. The average rate of palate fusion was 84% in vehicle controls. For compounds that are teratogenic in experimental animals in vivo, the fusion rates of palatal shelves decreased as the concentration of the test chemicals increased, showing a dose‐dependent relationship. Palate fusion was inhibited by 11 of the 15 in vivo teratogens, and the predictability of in vivo developmental toxicity in this culture system was 73%. Cyclophosphamide itself did not inhibit the growth and fusion of explanted palates, but supplementation of hepatic S‐9 fraction and cofactors for a monooxygenase system converted it to a toxic substance, as was shown in other in vitro systems. The 50% inhibitory concentration (IC50) value calculated based on the fusion rate was also found to be a useful parameter for evaluating the developmental toxicity of drugs. The teratogenic risk in the human fetus could be assessed by comparing the minimal toxic concentrations of the test compound on cultured palates with the maximal plasma level in pregnant women under therapeutic conditions and with the plasma concentrations when its minimal teratogenic dose is given to pregnant mice. This organ culture system of the fetal palate should be useful for screening the developmental toxicity of drugs and other environmental agents, and its value should increase when it is used in combination with other battery test systems.
Possible association between different congenital abnormalities and use of different sulfonamides during pregnancy
Authors: Czeizel Andrew E. , Puhó Erzsébet , T. Sørensen Henrik , Olsen Jørn
Published: May 2004

ABSTRACT  The objective of the study presented here was to check the debated human teratogenic potential of sulfonamide drugs. Five different sulfonamides such as sulfamethazine, sulfathiourea, sulfamethoxypyridazine, sulfamethoxydiazine and the combination of sulfamethazine‐sulfathiourea‐sulfamethoxypyridazine were differentiated.

Cases with congenital abnormalities were compared with their matched controls without congenital abnormalities in the population‐based large data set of the Hungarian Case‐Control Surveillance of Congenital Abnormalities between 1980 and 1996.

Of 38 151 newborn infants without any congenital abnormalities (control group), 163 (0.4%) had mothers who were treated with the sulfonamides studied during pregnancy, while of 22 843 cases with congenital abnormalities, 140 (0.6%) had mothers who were treated with the sulfonamides studied during pregnancy. The analysis of cases and matched controls indicated a higher rate of cardiovascular malformation (adjusted prevalence odds ratios [POR] with 95% CI: 3.5, 1.9–6.4) and clubfoot (adjusted POR with 95% CI: 2.6, 1.1–6.2) in infants born to mothers with sulfonamide treatment in the second and third months of pregnancy. The detailed analysis of different sulfonamides showed a possible association between cardiovascular malformations (adjusted POR with 95%; CI: 6.5, 2.6–15.9), particularly ventricular septal defect (17.1, 1.3–141.1) and sulfamethoxydiazine during the second and third months of pregnancy. In addition, a possible association was found between clubfoot and sulfathiourea, both during the entire pregnancy (adjusted POR with 95% CI: 2.3, 1.2–4.3) and in the second and third months of gestation (3.9, 1.1–13.8).

Thus, maternal treatment of sulfamethoxydiazine may cause ventricular septal defect, while sulfathiourea may induce clubfoot; however, further studies are needed to verify or reject these associations.
No sex differences in 18 trisomy births in the Kanagawa Birth Defects Monitoring Program
Authors: Kuroki Yoshikazu , Kurosawa Kenji
Published: May 2004

ABSTRACT  Trisomy 18 is a common chromosome anomaly. The predominance of female infants is widely accepted in the literature. This study clarified no sex differences in 18 trisomy births.
Prior serum- and AICAR-induced AMPK activation in primary human myocytes does not lead to subsequent increase in insulin-stimulated glucose uptake
Authors: Al-Khalili Lubna , Krook Anna , Zierath Juleen R. , Cartee Gregory D.
Published: May 2004

Exposing isolated rat skeletal muscle to 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside [AICAR, a pharmacological activator of AMP-activated protein kinase (AMPK)] plus serum leads to a subsequent increase in insulin-stimulated glucose transport (Fisher JS, Gao J, Han DH, Holloszy JO, and Nolte LA. Am J Physiol Endocrinol Metab 282: E18–E23, 2002). Our goal was to determine whether preincubation of primary human skeletal muscle cells with human serum and AICAR (Serum+AICAR) would also induce a subsequent elevation in insulin-stimulated glucose uptake. Cells were preincubated for 1 h under 4 conditions: 1) without AICAR or serum (Control), 2) with serum, 3) with AICAR, or 4) with Serum+AICAR. Some cells were then collected for immunoblot analysis to assess phosphorylation of AMPK (pAMPK) and its substrate acetyl-CoA carboxylase (ACC). Other cells were incubated for an additional 4 h without AICAR or serum and then used to measure basal or insulin-stimulated 2-deoxyglucose (2-DG) uptake. Level of pAMPK was increased ( P < 0.01) for myotubes exposed to Serum+AICAR vs. all other groups. Phosphorylated ACC (pACC) levels were higher for both Serum+AICAR ( P < 0.05) and AICAR ( P < 0.05) vs. Control and Serum groups. Basal ( P < 0.05) and 1.2 nM insulin-stimulated ( P < 0.005) 2-DG uptake was higher for Serum vs. all other preincubation conditions at equal insulin concentration. Regardless of insulin concentration (0, 1.2, or 18 nM), 2-DG was unaltered in cells preincubated with Serum+AICAR vs. Control cells. In contrast to results with isolated rat skeletal muscle, increasing the pAMPK and pACC in human myocytes via preincubation with Serum+AICAR was insufficient to lead to a subsequent enhancement in insulin-stimulated glucose uptake.
Overexpression of human β2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes
Authors: Grandy Scott A. , Denovan-Wright Eileen M. , Ferrier Gregory R. , Howlett Susan E.
Published: May 2004

This study investigated cardiac excitation-contraction coupling at 37°C in transgenic mice with cardiac-specific overexpression of human β2-adrenergic receptors (TG4 mice). In field-stimulated myocytes, contraction was significantly greater in TG4 compared with wild-type (WT) ventricular myocytes. In contrast, when duration of depolarization was controlled with rectangular voltage clamp steps, contraction amplitudes initiated by test steps were the same in WT and TG4 myocytes. When cells were voltage clamped with action potentials simulating TG4 and WT action potential configurations, contractions were greater with long TG4 action potentials and smaller with shorter WT action potentials, which suggests an important role for action potential configuration. Interestingly, peak amplitude of L-type Ca2+ current ( ICa-L) initiated by rectangular test steps was reduced, although the voltage dependencies of contractions and currents were not altered. To explore the basis for the altered relation between contraction and ICa-L, Ca2+ concentrations were measured in myocytes loaded with fura 2. Diastolic concentrations of free Ca2+ and amplitudes of Ca2+ transients were similar in voltage-clamped myocytes from WT and TG4 mice. However, sarcoplasmic reticulum (SR) Ca2+ content assessed with the rapid application of caffeine was elevated in TG4 cells. Increased SR Ca2+ was accompanied by increased frequency and amplitudes of spontaneous Ca2+ sparks measured at 37°C with fluo 3. These observations suggest that the gain of Ca2+-induced Ca2+ release is increased in TG4 myocytes. Increased gain counteracts the effects of decreased amplitude of ICa-L in voltage-clamped myocytes and likely contributes to increased contraction amplitudes in field-stimulated TG4 myocytes.
Upregulation of cardiovascular ghrelin receptor occurs in the hyperdynamic phase of sepsis
Authors: Wu Rongqian , Zhou Mian , Cui Xiaoxuan , Simms H. Hank , Wang Ping
Published: May 2004

Ghrelin, a newly identified endogenous ligand for growth hormone secretagogue receptor 1a (GHSR-1a, i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide. Although sepsis is characterized by an early, hyperdynamic phase, it remains unknown whether ghrelin or GHSR-1a plays a role in the cardiovascular response to sepsis. To determine this, polymicrobial sepsis was induced by cecal ligation and puncture in male adult rats. At 5 h (i.e., early sepsis) or 20 h (i.e., late sepsis) after cecal ligation and puncture, blood and tissue samples were collected. Ghrelin levels and ghrelin and GHSR-1a mRNA expression were assessed by RIA and RT-PCR, respectively. In addition, GHSR-1a protein levels in aorta, heart, and small intestine were determined by Western blotting. The vascular response to ghrelin was determined by using an isolated gut preparation. A primary rat aortic smooth muscle cell culture was used to determine the effects of LPS on GHSR-1a expression. The results indicate that although ghrelin levels decreased at early and late sepsis, its receptor was markedly elevated in early sepsis. Moreover, ghrelin-induced relaxation in resistance blood vessels of the isolated small intestine increased significantly during early sepsis but was not altered in late sepsis. Furthermore, GHSR-1a expression in smooth muscle cells was significantly increased at mRNA and protein levels with stimulation by LPS at 10 ng/ml. These results demonstrate that GHSR-1a expression is upregulated and vascular sensitivity to ghrelin stimulation is increased in the hyperdynamic phase of sepsis.
Effects of anesthetics on systemic hemodynamics in mice
Authors: Janssen Ben J. A. , De Celle Tijl , Debets Jacques J. M. , Brouns Agnieszka E. , Callahan Michael F. , Smith Thomas L.
Published: May 2004

The aim of this study was to compare the systemic hemodynamic effects of four commonly used anesthetic regimens in mice that were chronically instrumented for direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and C57BL6 strains) were instrumented with a transit-time flow probe placed around the ascending aorta for CO measurement. An arterial catheter was inserted into the aorta 4 or 5 days later for blood pressure measurements. After full recovery, hemodynamic parameters including stroke volume, heart rate, CO, mean arterial pressure (MAP), and total peripheral resistance were measured with animals in the conscious state. General anesthesia was then induced in these mice using isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The doses and routes of administration of these agents were given as required for general surgical procedures in these animals. Compared with the values obtained for animals in the conscious resting state, MAP and CO decreased during all anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, −24 ± 3%; CO, −5 ± 7%; n = 15 mice) and greatest for K-X (MAP, −51 ± 6%; CO, −37 ± 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully antagonized by administration of the α2-receptor antagonist atipamezole ( n = 8 mice). These results indicate that the anesthetic Iso has fewer systemic hemodynamic effects in mice than the nonvolatile anesthetics.
Na-K-2Cl cotransporter inhibition impairs human lung cellular proliferation
Authors: Iwamoto Lynn M. , Fujiwara Naomi , Nakamura Kenneth T. , Wada Randal K.
Published: May 2004

The widespread presence of the Na-K-2Cl (NKCC) cotransporter protein suggests that chronic administration of inhibitors may result in adverse effects. Inhibition of the NKCC cotransporter by loop diuretics is felt to underlie the diuretic and the pulmonary smooth muscle relaxant effects of this drug class. However, the fundamental regulation of salt and water movement by this cotransporter suggests that it may also mediate cell volume changes occurring during cell cycle progression. Thus we hypothesized that NKCC cotransporter inhibition by loop diuretics would decrease cellular proliferation. Normal human bronchial smooth muscle cells (BSMC) showed a significant concentration-dependent decrease in cell counts after 7 days of exposure to both bumetanide ( n = 5–10) and furosemide ( n = 6–16) compared with controls. Proliferation was similarly inhibited in normal human lung fibroblasts ( n = 5–9). To determine whether this was due to loss of cells, we performed apoptosis assays on BSMC. Both annexin V-propidium iodide staining ( n = 5–10) and single cell gel electrophoresis assays ( n = 4) were negative for necrosis and apoptosis in BSMC exposed to 10 μM bumetanide. Subsequent analysis of the cell cycle by flow cytometry showed that bumetanide-exposed BSMC were delayed in G1 phase compared with controls ( n = 4–8). This is the first evidence for loop diuretic inhibition of airway smooth muscle cell proliferation. NKCC cotransporter inhibition impeded G1-S phase transition without facilitating cell death. Thus although inhibition by loop diuretics relaxes airway smooth muscle, the NKCC cotransporter may have a more important role in cell proliferation regulation.
Effect of changing the gravity vector on respiratory output and control
Authors: Dellacá R. L. , Bettinelli D. , Kays C. , Techoueyres P. , Lachaud J. L. , Vaïda P. , Miserocchi G.
Published: May 2004

We studied the respiratory output in five subjects exposed to parabolic flights [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)] and when switching from sitting to supine (legs bent at the knees). Despite differences in total respiratory compliance (highest at 0 Gz and in supine and minimum at 1.8 Gz), no significant changes in elastic inspiratory work were observed in the various conditions, except when comparing 1.8 Gz with 1 Gz (subjects were in the seated position in all circumstances), although the elastic work had an inverse relationship with total respiratory compliance that was highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz, lung resistance (airways plus lung tissue) increased significantly by 52% in the supine but slightly decreased at 0 Gz. We calculated, for each condition, the tidal volume changes based on the energy available in the preceding phase and concluded that an increase in inspiratory muscle output occurs when respiratory load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes, ventilation increased, going to 1.8 and 0 Gz (up to ≈23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately −14%), shifting to supine posture (transition time ∼15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties.
Myogenic protein expression before and after resistance loading in 26- and 64-yr-old men and women
Authors: Bamman Marcas M. , Ragan Ronald C. , Kim Jeong-su , Cross James M. , Hill Vernishia J. , Tuggle S. Craig , Allman Richard M.
Published: May 2004

Based on the growing body of evidence implicating an important role for myogenic regulatory factors (MRFs) in the adaptive responses of skeletal muscle to mechanical load, we tested the hypothesis that protein concentrations of MRFs as well as cell cycle proteins (i.e., cyclins and cyclin-dependent kinase inhibitors) would be altered after heavy leg resistance exercise (RE). Because we and others, however, have shown a blunted adaptive response to long-term resistance training in older (O) women [females (F)] compared with men (M), we also tested the hypothesis that these myogenic responses to RE would be influenced by age and gender. Twenty-two younger (Y) adults (20–35 yr, 11 YF, 11 YM) and 20 O adults (60–75 yr, 9 OF, 11 OM) consented to vastus lateralis muscle biopsy before and 24 h after a bout of RE using a regimen known to induce myofiber hypertrophy when performed 2–3 days/wk for several weeks (3 sets of 80% one-repetition maximum for squat, leg press, and knee extension). Protein concentrations of MRFs (MyoD, myogenin, myf-6), cyclin D1, cyclin B1, α-actin, and the cyclin-dependent kinase inhibitor p27kip were determined by immunoblotting. Data were analyzed by using age × gender × load repeated-measures ANOVA. Myogenin expression was 44% higher ( P < 0.05) in O compared with Y, and myf-6 tended to be higher in OF compared with YF (95%, P = 0.059). A significant gender × load interaction indicated that, in F, RE led to a reduction in p27kip (20%; P < 0.05), which was driven mainly by a 27% drop in OF. Levels of cyclin D1, cyclin B1, MyoD, myf-6, and α-actin were not influenced by age, gender, or loading. We report a novel finding in humans of markedly higher myogenin protein content in older sedentary muscle. The results do not, however, support the hypothesis that myogenic protein expression is altered 24 h after RE, irrespective of age or gender. Although the time point of postexercise muscle biopsy could be viewed as too early to capture maximal effects for most of these proteins, the significant decline in p27kip concentration found in OF suggests that mechanical load may provide one means of overcoming the inhibitory influence of p27kip.
Differences Between Accumbens Core and Shell Neurons Exhibiting Phasic Firing Patterns Related to Drug-Seeking Behavior During a Discriminative-Stimulus Task
Authors: Ghitza Udi E. , Fabbricatore Anthony T. , Prokopenko Volodymyr F. , West Mark O.
Published: May 2004

The habit-forming effects of abused drugs depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens (NAcc). To examine whether different NAcc subterritories (core and medial shell) exhibit a differential distribution of neurons showing phasic firing patterns correlated with drug-seeking behavior, rats were trained to self-administer cocaine, and activity of single NAcc neurons was recorded. In the presence of a discriminative-stimulus (SD) tone, a single lever press produced an intravenous infusion of cocaine (0.35 mg/kg), terminated the tone, and started an intertone interval ranging from 3 to 6 min. Lever presses during this intertone interval had no programmed consequences. In addition to evaluating neuronal firing patterns associated with cocaine-reinforced presses, we also evaluated firing patterns associated with unreinforced lever presses to allow interpretation of firing free of factors other than the instrumental response (such as tone-off and onset of the pump signaling drug infusion). Core neurons exhibited a greater change in firing than medial shell neurons both in the seconds preceding the reinforced and unreinforced lever press response and in the seconds following the unreinforced response. Core and medial shell neurons exhibited similar changes in firing during the seconds following the cocaine-reinforced press. The differential distribution of neurons exhibiting phasic changes in firing preceding the lever press suggests that the physiological activity of core neurons may play a greater role than that of medial shell neurons in processes related to the execution of conditioned drug-seeking responses.
Existence of mild solutions of second‐order neutral functional differential inclusions with nonlocal conditions in Banach spaces
Authors: Anthoni S. Marshal , Kim J.-H. , Dauer J. P.
Published: May 2004

We study the existence of mild solutions of the nonlinear second‐order neutral functional differential and integrodifferential inclusions with nonlocal conditions in Banach spaces. The results are obtained by using the theory of strongly continuous cosine families of bounded linear operators and a fixed point theorem for condensing maps due to Martelli.
Mutation in the
KCNQ1
Gene Leading to the Short QT-Interval Syndrome
Authors: Bellocq Chloé , van Ginneken Antoni C.G. , Bezzina Connie R. , Alders Mariel , Escande Denis , Mannens Marcel M.A.M. , Baró Isabelle , Wilde Arthur A.M.
Published: May 2004

Background—

The electrocardiographic short QT-interval syndrome forms a distinct clinical entity presenting with a high rate of sudden death and exceptionally short QT intervals. The disorder has recently been linked to gain-of-function mutation in
KCNH2
. The present study demonstrates that this disorder is genetically heterogeneous and can also be caused by mutation in the
KCNQ1
gene.

Methods and Results—

A 70-year man presented with idiopathic ventricular fibrillation. Both immediately after the episode and much later, his QT interval was abnormally short without any other physical or electrophysiological anomalies. Analysis of candidate genes identified a g919c substitution in
KCNQ1
encoding the K
+
channel KvLQT1. Functional studies of the KvLQT1 V307L mutant (alone or coexpressed with the wild-type channel, in the presence of IsK) revealed a pronounced shift of the half-activation potential and an acceleration of the activation kinetics leading to a gain of function in
I
Ks
. When introduced in a human action potential computer model, the modified biophysical parameters predicted repolarization shortening.

Conclusions—

We present an alternative molecular mechanism for the short QT-interval syndrome. Functional and computational studies of the
KCNQ1
V307L mutation identified in a patient with this disorder favor the association of short QT with mutation in
KCNQ1
.
Stress Wave Propagation Effects in Two- and Three-Layered Composite Materials
Authors: Tasdemirci A. , Hall I. W. , Gama B. A. , Guden M.
Published: May 2004

Multilayer materials consisting of ceramic and glass/epoxy composites have been subjected to high strain rate compression testing using the Split Hopkinson Pressure Bar. The samples were extensively strain gaged so that dynamic data were generated directly from the samples during testing. Output data from the experiments were compared with numerical simulations of the same experiments and good agreement was noted. It was found that the stress distribution within samples was quite inhomogeneous and that stresses were highest in the region of the bar-sample interface. The presence of a rubber interlayer between the ceramic and glass/epoxy decreased the stress in both components but dramatically increased the degree of stress in homogeneity.
Interlaminar Stress Concentrations in Layered Structures: Part II - Closed-Form Analysis of Stresses at Laminated Rectangular Wedges with Arbitrary Non-Orthotropic Layup
Authors: Mittelstedt Christian , Becker Wilfried
Published: May 2004

In the second of a series of two papers, a refined closed-form analysis method for the calculation of interlaminar stress concentrations in the vicinity of rectangular wedges of thermally loaded composite laminates with arbitrary layup is presented. Based on adequate layerwise shape assumptions for the in-plane components of Cauchy’s stress tensor that automatically fulfill the conditions of traction free edges, the interlaminar stresses are derived from the three-dimensional equilibrium conditions in combination with the exact fulfillment of the given homogeneous boundary conditions of traction-free laminate facings and the requirement of continuity of the interlaminar stresses at the ply interfaces. The far field conditions of recovery of the stress results by classical laminate plate theory in the inner laminate regions with increasing distance from the laminate corner are accounted for. Free constants in the stress shape functions are determined by the minimization of the laminate’s complementary potential energy which can be accomplished in an iterative manner. The stress shape functions are assumed as simple exponential terms with respect to the in-plane coordinates, whereas polynomials are applied as thickness functions. The present analysis methodology is found to be in good agreement with finite-element computations and yields reasonably accurate results with little computational effort.
Formations for Fast Locomotion of Metamorphic Robotic Systems
Authors: Dumitrescu Adrian , Suzuki Ichiro , Yamashita Masafumi
Published: May 2004

In this paper, we examine the problem of dynamic self-reconfiguration of a modular robotic system (frequently referred to as a self-reconfigurable or metamorphic system), to a formation aimed at reaching a specified target position as quickly as possible. We present a number of fast formations for both rectangular and hexagonal systems, and prove upper and lower bounds on the speed of locomotion. In particular, the formations presented here achieve a constant ratio guarantee on the time to reach a given target in the asymptotic sense.
A Novel Fully Decoupled Two-Degrees-of-Freedom Parallel Wrist
Authors: Carricato Marco , Parenti-Castelli Vincenzo
Published: May 2004

In this paper we present a novel pointing parallel mechanism with fully decoupled degrees of freedom. The mechanism consists of two interconnected slider-crank linkages, each one of which independently actuates one of the Euler angles of the output link. Motors can be mounted on the frame. The parallel architecture provides the mechanism with compactness and robustness, while decoupling of motion guarantees a wide workspace, an easy mathematical treatment, and a simple control. Such a mechanism may be suitable for applications that require aiming bodies such as tools, telescopes, antennas, cameras, solar panels, human or humanoid artificial limbs, particularly if requisites on dimensions and stoutness on the one hand and mobility on the other are stringent.
Synthesis of Reactionless Spatial 3-DoF and 6-DoF Mechanisms without Separate Counter-Rotations
Authors: Wu Yangnian , Gosselin Clément M.
Published: May 2004

In this paper we present the synthesis of novel reactionless spatial three-degrees-of-freedom (3-DoF) and 6-DoF mechanisms without any separate counter-rotation, using four-bar linkages. Based on the conditions of dynamic balancing of a single planar four-bar linkage developed elsewhere, the spatial problem is shown to be equivalent to ensuring that the inertia tensor of reactionless four-bar linkage(s), which is(are) attached on the moving link of a reactionless four-bar linkage, remains constant while moving. The reactionless conditions for planar four-bar linkages undergoing spatial motion are first given. Then, reactionless spatial 3-DoF mechanisms using four-bar linkages are synthesized. A numerical example of the reactionless spatial 3-DoF mechanism is given and, with the help of the dynamic simulation software ADAMS, it is shown that the mechanism is reactionless for arbitrary trajectories. Finally, this mechanism is used to synthesize reactionless 6-DoF parallel mechanisms.
Closure and Quality Equivalence for Efficient Synthesis of Grasps from Examples
Authors: Pollard Nancy S.
Published: May 2004

One goal of grasp selection for robotics is to choose contact points that guarantee properties such as force- or form-closure. Many efficient algorithms have been developed to address this problem, but most of these algorithms focus on grasps having a minimal number of contact points. Increasing the number of contacts can dramatically improve the quality and flexibility of grasps that are constructed. However, computation time becomes a problem, as grasp synthesis algorithms that can be generalized to an arbitrary number of contacts typically require time exponential in the number of contacts. This paper presents an efficient algorithm for synthesis of many-contact grasps. The key idea is to geometrically construct families of grasps around a single example such that all grasps within a family meet user-specified design goals. We show that our construction technique can be used to form force-closure grasps, partial force-closure grasps, and grasps above a quality threshold. Our approach requires time polynomial in the number of contacts, making it feasible to handle grasps with relatively large numbers of contacts. Results are shown for three-dimensional grasps with friction having five to twelve contacts and specialized for a variety of tasks. We have used this approach to design grasps for a robot hand and quasi-static manipulation plans for a humanoid robot.
Experimental Validation of a Framework for the Design of Controllers that Induce Stable Walking in Planar Bipeds
Authors: Westervelt E. R. , Buche G. , Grizzle J. W.
Published: May 2004

In this paper we present the experimental validation of a framework for the systematic design, analysis, and performance enhancement of controllers that induce stable walking in N -link underactuated planar biped robots. Controllers designed via this framework act by enforcing virtual constraints—holonomic constraints imposed via feedback—on the robot’s configuration, which create an attracting two-dimensional invariant set in the full walking model’s state space. Stability properties of resulting walking motions are easily analyzed in terms of a two-dimensional subdynamic of the full walking model. A practical introduction to and interpretation of the framework is given. In addition, in this paper we develop the ability to regulate the average walking rate of the biped to a continuum of values by modification of within-stride and stride-boundary characteristics, such as step length.