bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased O2 Consumption and Energy Loss in Premature Infants following Medical Care Procedures
Authors: Yeh Tsu F. , Lilien Lawrence D. , Leu Shis T. , Pildes Rosita S.
Published: September 2009

Oxygen consumption (VO2) and CO2 production (VCO2) were measured continuously for 24 h in 10 premature infants during their ongoing nursing care. Using a flow-through technique, the total VO2 and VCO2 over a given period of time were determined from the area under the O2- and CO2-concentration-time curve of the mixed expired gas. Following chest physiotherapy, heel stick and i.v. needle insertion, there was a significant (p < 0.01) increase in VO2 and VCO2. When measured for 24 h, the total daily increase of VO2 attributed to these procedures ranged from 2.1 to 11.7% of total daily VO2 equivalent to an estimated energy loss of 0.6–4.1 kcal/kg/day.
Fetal Adaptations to Spontaneous Hypoxemia and Responses to Maternal Oxygen Breathing
Authors: Goetzman Boyd W. , Itskovitz Joseph , Rudolph Abraham M.
Published: September 2009

Circulatory adaptations to spontaneous hypoxemia were assessed with the microsphere method at 119–123 days gestation in ovine fetuses who were subsequently found to be growth retarded. Combined ventricular output tended to be increased and it was redistributed so that oxygen delivery to the heart was increased by over 50%, oxygen delivery to the lung and placenta were decreased, and that to other organs, including the brain, were maintained. Maternal oxygen breathing for 1 h not only reversed these adaptations, but also produced an augmented lung blood flow. Umbilical blood flow was not affected. These findings have clinical implications for the growth-retarded fetus about to undergo the stress of labor.
Effects of Fetal Decapitation upon Porcine Placental Metabolism
Authors: Ramsay T.G. , Sheahan J.A. , Hausman G.J. , Martin R.J.
Published: September 2009

This experiment was performed to determine if the fetus can influence its placental metabolism. Fetal pigs were decapitated at 45 days of gestation and their placentas compared at 110 days to within litter controls. No histological or histochemical differences were observed. Glycogen levels were elevated in the fetal placenta of decapitated pigs by 107%. Fatty acid synthesis was increased in the fetal placenta of decapitated animals (12.9 ± 1.5 vs. 3.4 ± 0.7 nmol acetate units/100 mg/2 h). Fetal decapitation increased fetal placental fatty acid esterification by 43% and oxidation by 125%. The altered lipid metabolism of the fetal placenta was reflected in enzymes associated with substrate utilization (pyruvate kinase and lactate dehydrogenase). Maternal placenta lipogenesis was also altered by fetal manipulation. Leucine conversion to its alpha ketoacid was increased in the fetal placenta of the decapitated pigs (14.8 ± 1.7 vs. 8.6 ± 1.4 nmol/100 mg/2 h) indicating amino acid metabolism was affected by this treatment. The ability of an altered fetal endocrinology and metabolism to affect the placental metabolism supports the concept of a fetal influence on placental metabolism.
Effect of Neonatal Cerebrospinal Fluid on Monocyte Chemotaxis
Authors: Pappu Lakshmi D. , Levkoff Abner H. , Shannon Barry T. , Loadholt Claude B.
Published: September 2009

We have reported in our previous study that macrophages constitute 58% of the total number of white cells in noninfected neonatal cerebrospinal fluid (CSF). CSF macrophages are probably derived from blood monocytes. To explain their predominance, we compared the chemotactic response of monocytes from cord and adult blood to neonatal (NCSF) and non-neonatal spinal fluids (NNCSF). Zymosan-activated serum (ZAS) was used as a positive control. Significance was accepted as p ≤ 0.05. We observed that both random migratory (RM) activity and chemotactic responses (CM) of cord monocytes to neonatal CSF and ZAS were greater than those of monocytes obtained from adult blood, resulting in a significant increase in the chemotactic differential (CD). Chemotactic responses of neonatal monocytes were significantly greater in the presence of neonatal CSF as compared to CSF from older children as indicated by CD. The CD of neonatal monocytes to neonatal CSF was greater than that of neonatal neutrophils. These findings are consistent with the presence of specific monocyte chemotaxins in noninfected neonatal CSF.
Separate Effects of Fatty Acid Oxidation and Glucagon on Gluconeogenesis in Isolated Hepatocytes from Newborn Pigs
Authors: Duée P.H. , Pégorier J.P. , Peret J. , Girard J.
Published: September 2009

In hepatocytes isolated from 48-hour-old suckling pigs, the inhibition of endogenous fatty acid oxidation leads to a 30% inhibition of glucose production from lactate. Addition of oleate plus carnitine to hepatocytes from 48-hour-old fasting pigs increases by 30% the rate of gluconeogenesis from lactate. In hepatocytes isolated from fasting newborn pigs, addition of glucagon (0.5 ng/ml) produces a 30% increase in the rate of glucose production from lactate and a 70% increase of glucose synthesis from dihydroxyacetone. The high rate of lactate plus pyruvate production in fasting piglets is markedly suppressed by glucagon and return to the value measured in suckling newborns. Combined addition of oleate and glucagon to hepatocytes from fasting piglets increases by 2-fold the rate of glucose production from lactate but does not restore totally the rate of glucose synthesis found in suckling piglets. It is concluded that fatty acid oxidation and hormonal environment contribute significantly to the development of an active gluconeogenesis in the newborn pig but do not represent the sole factors involved in the regulation of hepatic gluconeogenesis.
Effect of Fetal Decapitation on Unbound Rat Plasma Corticosterone Concentration at the End of Pregnancy
Authors: Cohen Alia , Guillon Yveline
Published: September 2009

In normal fetuses from day 16 to 21 of pregnancy, unbound plasma corticosterone concentration increases slowly from day 16 to 17, and rapidly from day 17 to 19, remaining high until birth. Fetal decapitation on day 18 produces a fall in unbound plasma corticosterone only when the mother is adrenalectomized. The ability of corticosterone to cross the placental barrier from mother to fetus or inversely is discussed.
Intestinal Transmission of Macromolecules (BSA and FITC-Dextran) in the Neonatal Pig: Enhancing Effect of Colostrum, Proteins and Proteinase Inhibitors
Authors: Weström B.R. , Ohlsson B.G. , Svendsen J. , Tagesson C. , Karlsson B.W.
Published: September 2009

The effects of colostrum and constituents/factors in colostrum which may influence intestinal macromolecular transmission in the newborn preclosure pig were investigated. Unsuckled piglets were given, by use of a stomach tube, bovine serum albumin (BSA) and fluorescein-isothiocyanate (FΙTC)-labelled dextran 70,000 (FITC-D) as markers together with colostrum or the factors under study. The serum levels of BSA and FITC-D 4 h after feeding were then determined as a measure of the transfer. It was found that the two colos-trums tested, bovine and especially porcine, markedly enhanced the transmission of both BSA and FITC-D. Furthermore, increasing amounts of the model proteins, BSA and bovine IgG (50–200 mg/ml), significantly increased the transfer of FITC-D, whereas unlabelled dextran 70,000 given in similar amounts did not. Proteinase inhibitors obtained from sow colostrum or soy bean also enhanced the transmission of both BSA and FITC-D while the inactive inhibitors, given as trypsin-inhibitor complexes, had no effect. On the other hand, addition of a proteinase, porcine trypsin, significantly decreased the transmission of FITC-D. These findings indicate that the intestinal transmission of macromolecules in the preclosure piglet is governed by the amount of protein available in the intestine. Therefore, feeding colostrum with a high protein content and proteinase inhibitors is likely to favour efficient intestinal transmission, although other colostrum factors may also be of importance.
Growth Hormone Responses to Growth Hormone Releasing Factor in Neonates
Authors: Shimano Satoshi , Suzuki Shigeyoshi , Nagashima Kanji , Yagi Hideki , Sakaguchi Masao , Kuroume Takayoshi
Published: September 2009

The response of growth hormone (GH) to synthetic human growth hormone releasing factor (hGRF) administered intravenously was examined in 32 neonates aged 3–28 days. GH peaked at 30 min after hGRF administration and the mean ± SEM level of GH at maximal response was 66.4 ± 6.2 ng/ml. In the comparison between the neonates less than 7 days old and those more than 8 days old, between the neonates less than 37 weeks and those more than 38 weeks in gestational age, between the neonates under 2,500 g and those over 2,501 g in birth body weight, and between males and females, no significant statistical differences were observed.
Value of 123I-MIBG Scintigraphy in Paraganglioma
Authors: Milardovic Renata , Corssmit Eleonora P.M. , Stokkel Marcel
Published: September 2009

Aim: The aim of the study was to evaluate the current role of 123I-MIBG scintigraphy in the detection and follow-up of patients with paragangliomas. Materials and Methods: 117 patients were referred for diagnostic 123I-MIBG scintigraphy based on a strong clinical suspicion, positive familial history and genetic testing, or for follow-up of paragangliomas.123I-MIBG images were analyzed and correlated with 111In-octreotide scintigraphy, CT or MRI results. Accuracy of the imaging method was calculated per patient and per tumor per site. Results: A total of 117 patients were referred for 123I-MIBG diagnostic imaging; 80 patients were diagnosed with paraganglioma; 66 patients had a single neuroendocrine tumor and 14 patients multiple tumors. The total number of all lesions in these patients was 172. 123I-MIBG scintigraphy demonstrated 65 lesions in 56 patients (overall sensitivity: 56.3%, specificity: 84%). Lesion-per-site analysis revealed that sensitivity and specificity significantly varied per tumor site (lowest sensitivity for the head and neck: 17.5% and lowest specificity for the abdomen: 87.5%). Hormones were elevated in 85 patients: 55 123I-MIBG tumors were positive and 35 tumors were negative. In 16 patients (13.7%) with a genetic burden and a single neuroendocrine tumor, 123I-MIBG whole-body imaging was successful at detecting a second tumor. In 2 patients (1.7%) with paragangliomas, 123I-MIBG unexpectedly detected metastases, so the restaging was properly done. Conclusion:123I-MIBG scintigraphy remains important in pheochromocytoma and functioning neuroendocrine tumors. The value of 123I-MIBG scintigraphy is high in familial syndromes with multiple neuroendocrine tumors at different sites, multifocal tumors, and relapsing and metastatic disease.
Proteomics of Apolipoproteins and Associated Proteins From Plasma High-Density Lipoproteins
Authors: Davidsson Pia , Hulthe Johannes , Fagerberg Björn , Camejo Germán
Published: September 2009

Proteomics studies have extended the list of identified apolipoproteins and associated proteins present in HDL and its subclasses. These proteins appear to cluster around specific functions related to lipid metabolism, inflammation, the immune system, hormone-binding, hemostasis, and antioxidant properties. Small studies suggest that there are substantial differences between the HDL proteome from cardiovascular disease patients and that from controls. Furthermore, dyslipidemia therapy shifts the HDL proteome from patients toward the profile observed in healthy controls. In addition, the proteome of HDL and LDL from patients with insulin resistance and peripheral atherosclerosis show significant differences with that of matched healthy controls. The proteome of HDL and LDL density subclasses have apolipoproteins and associated proteins profiles that suggest subclass-specific functions. However, proteomics studies of lipoproteins are few and small and should be interpreted with caution. Nonetheless rapid technical progress in proteomic platforms suggest that soon analysis time will be reduced and precise measurement of identified proteins will be possible. This, combined with controlled purification steps of HDL and its subclasses should provide further information about proteins involved in the particles postulated spectrum of functions, including those believed to be atheroprotective.
The ADMA/DDAH Pathway Regulates VEGF-Mediated Angiogenesis
Authors: Fiedler Lorna R , Bachetti Tiziana , Leiper James , Zachary Ian , Chen Lihua , Renné Thomas , Wojciak-Stothard Beata
Published: September 2009

Objectives—

Asymmetrical dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor and cardiovascular risk factor associated with angiogenic disorders. Enzymes metabolising ADMA, dimethylarginine dimethylaminohydrolases (DDAH) promote angiogenesis, but the mechanisms are not clear. We hypothesized that ADMA/DDAH modifies endothelial responses to vascular endothelial growth factor (VEGF) by affecting activity of Rho GTPases, regulators of actin polymerization, and focal adhesion dynamics.

Methods and Results—

The effects of ADMA on VEGF-induced endothelial cell motility, focal adhesion turnover, and angiogenesis were studied in human umbilical vein endothelial cells (HUVECs) and DDAH I heterozygous knockout mice. ADMA inhibited VEGF-induced chemotaxis in vitro and angiogenesis in vitro and in vivo in an NO-dependent way. ADMA effects were prevented by overexpression of DDAH but were not associated with decreased proliferation, increased apoptosis, or changes in VEGFR-2 activity or expression. ADMA inhibited endothelial cell polarization, protrusion formation, and decreased focal adhesion dynamics, resulting from Rac1 inhibition after decrease in phosphorylation of vasodilator stimulated phosphoprotein (VASP). Constitutively active Rac1, and to a lesser extent dominant negative RhoA, abrogated ADMA effects in vitro and in vivo.

Conclusion—

The ADMA/DDAH pathway regulates VEGF-induced angiogenesis in an NO- and Rac1-dependent manner.
Adaptive and Maladptive Effects of SMAD3 Signaling in the Adult Heart After Hemodynamic Pressure Overloading
Authors: Divakaran Vijay , Adrogue Julia , Ishiyama Masakuni , Entman Mark L. , Haudek Sandra , Sivasubramanian Natarajan , Mann Douglas L.
Published: September 2009

Background—

Previous studies suggest that transforming growth factor-β provokes cardiac hypertrophy and myocardial fibrosis; however, it is unclear whether the deleterious effects of transforming growth factor-β signaling are conveyed through SMAD-dependent or SMAD-independent signaling pathways.

Methods and Results—

To determine the contribution of SMAD-dependent signaling to cardiac remodeling, we performed transaortic constriction in SMAD3 null (SMAD3
−/−
) and littermate control mice (age, 10 to 12 weeks). Cumulative survival 20 days after transaortic constriction was significantly less in the SMAD3
−/−
mice when compared with littermate controls (43.6% versus 90.9%,
P
<0.01). Transaortic constriction resulted in a significant increase in cardiac hypertrophy in the SMAD3
−/−
mice, denoted by an increase in the heart weight to tibial length ratio and increased myocyte cross-sectional area. Loss of SMAD3 signaling also resulted in a significant 60% decrease in myocardial fibrosis (
P
<0.05). A microRNA microarray showed that 55 microRNAs were differentially expressed in littermate and SMAD3
−/−
mice and that 10 of these microRNAs were predicted to bind to genes that regulate the extracellular matrix. Of these 10 candidate microRNAs, both miR-25 and miR-29a were sufficient to decrease collagen gene expression when transfected into isolated cardiac fibroblasts in vitro.

Conclusions—

The results suggest that SMAD3 signaling plays dual roles in the heart: one beneficial role by delimiting hypertrophic growth and the other deleterious by modulating myocardial fibrosis, possibly through a pathway that entails accumulation of microRNAs that decrease collagen gene expression.
Reverse Epidemiology in Systolic and Nonsystolic Heart Failure
Authors: Güder Gülmisal , Frantz Stefan , Bauersachs Johann , Allolio Bruno , Wanner Christoph , Koller Michael T. , Ertl Georg , Angermann Christiane E. , Störk Stefan
Published: September 2009

Background—

Observational studies indicate that classical cardiovascular risk factors as body mass index, total cholesterol, and systolic blood pressure are associated with improved rather than impaired survival in heart failure (“reverse epidemiology”). We estimated the prognostic role of these risk factors in unselected patients with heart failure.

Methods and Results—

Consecutive subjects with heart failure of any cause and severity were enrolled (n=867), and survivors were followed for a median period of 594 days (25th to 75th percentile, 435 to 840). Mean age was 70�13 years, 41% were female, New York Heart Association class distribution I through IV was 15%/29%/41%/15%, and 49% had preserved left ventricular ejection function. At follow-up, 34% of the patients had died. Low levels of any risk factor (ie, body mass index, total cholesterol, and systolic blood pressure in the low tertile) indicated the highest mortality risk. After adjustment for age, sex, New York Heart Association class, and ejection fraction, ≥2 risk factors in the high tertile indicated a relative reduction in mortality risk of 51% (hazard ratio, 0.49; 95% CI, 0.35 to 0.68;
P
=0.001) compared with subjects with 3 risk factors in the low tertile. Further adjustment for cause of heart failure, relevant comorbidities, medication, and biomarkers attenuated this association only modestly (hazard ratio, 0.63; 95% CI, 0.45 to 0.89;
P
=0.009).

Conclusion—

In patients with heart failure, mortality risk counterintuitively increased on a cumulative scale with lower levels of body mass index, total cholesterol, and systolic blood pressure, irrespective of the type and severity of heart failure. Future studies need to identify whether risk factor control as presently recommended should be advocated in all patients with heart failure.
Association of Blood Pressure at Hospital Discharge With Mortality in Patients Diagnosed With Heart Failure
Authors: Lee Douglas S. , Ghosh Nina , Floras John S. , Newton Gary E. , Austin Peter C. , Wang Xuesong , Liu Peter P. , Stukel Thérèse A. , Tu Jack V.
Published: September 2009

Background—

Higher blood pressure in acute heart failure has been associated with improved survival; however, the relationship between blood pressure and survival in stabilized patients at hospital discharge has not been established.

Methods and Results—

In 7448 patients with heart failure (75.2�11.5 years; 49.9% men) discharged from the hospital in Ontario, Canada, we examined the association of systolic blood pressure (SBP) and diastolic blood pressure with long-term survival. Parametric survival analysis was performed, and survival time ratios were determined according to discharge blood pressure group. A total of 25 427 person-years of follow-up were examined. In those with left ventricular ejection fraction ≤40%, median survival was decreased by 17% (survival time ratio, 0.83; 95% CI, 0.71 to 0.98;
P
=0.029) when discharge SBP was 100 to 119 mm Hg and decreased by 23% (survival time ratio, 0.77; 95% CI, 0.62 to 0.97;
P
=0.024) when discharge SBP was <100 mm Hg, compared with those in the reference range of 120 to 139 mm Hg. Survival time ratios were 0.75 (95% CI, 0.60 to 0.92;
P
=0.007) and 0.75 (95% CI, 0.53 to 1.07;
P
=0.12) when discharge SBPs were 140 to 159 and ≥160 mm Hg, respectively. In those with left ventricular ejection fraction >40%, survival time ratios were 0.69 (95% CI, 0.51 to 0.93), 0.83 (95% CI, 0.71 to 0.99), 0.95 (95% CI, 0.80 to 1.14), and 0.76 (95% CI, 0.61 to 0.95) for discharge SBPs <100, 100 to 119, 140 to 159, and ≥160 mm Hg, respectively.

Conclusions—

In this long-term population-based study of patients with heart failure, the association of discharge SBP with mortality followed a U-shaped distribution. Survival was shortened in those with reduced or increased values of discharge SBP.
Differences in the Evolution of the Ischemic Penumbra in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats
Authors: McCabe Christopher , Gallagher Lindsay , Gsell Willy , Graham Delyth , Dominiczak Anna F. , Macrae I. Mhairi
Published: September 2009

Background and Purpose—

Stroke-prone spontaneously hypertensive rats (SHRSP) are a highly pertinent stroke model with increased sensitivity to focal ischemia compared with the normotensive reference strain (Wistar-Kyoto rats; WKY). Study aims were to investigate temporal changes in the ischemic penumbra in SHRSP compared with WKY.

Methods—

Permanent middle cerebral artery occlusion was induced with an intraluminal filament. Diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging was performed from 1 to 6 hours after stroke, with the PWI-DWI mismatch used to define the penumbra and thresholded apparent diffusion coefficient (ADC) maps used to define ischemic damage.

Results—

There was significantly more ischemic damage in SHRSP than in WKY from 1 to 6 hours after stroke. The perfusion deficit remained unchanged in WKY (39.9±6 mm
2
at 1 hour, 39.6±5.3 mm
2
at 6 hours) but surprisingly increased in SHRSP (43.9±9.2 mm
2
at 1 hour, 48.5±7.4 mm
2
at 6 hours;
P
=0.01). One hour after stroke, SHRSP had a significantly smaller penumbra (3.4±5.8 mm
2
) than did WKY (9.7±3.8,
P
=0.03). In WKY, 56% of the 1-hour penumbra area was incorporated into the ADC lesion by 6 hours, whereas in SHRSP, the small penumbra remained static owing to the temporal increase in both ADC lesion size and perfusion deficit.

Conclusions—

First, SHRSP have significantly more ischemic damage and a smaller penumbra than do WKY within 1 hour of stroke; second, the penumbra is recruited into the ADC abnormality over time in both strains; and third, the expanding perfusion deficit in SHRSP predicts more tissue at risk of infarction. These results have important implications for management of stroke patients with preexisting hypertension and suggest ischemic damage could progress at a faster rate and over a longer time frame in the presence of hypertension.
Stroke Patient Outcomes in US Hospitals Before the Start of the Joint Commission Primary Stroke Center Certification Program
Authors: Lichtman Judith H. , Allen Norrina B. , Wang Yun , Watanabe Emi , Jones Sara B. , Goldstein Larry B.
Published: September 2009

Background and Purpose—

The Joint Commission (JC) began certifying Primary Stroke Centers in November 2003. Cross-sectional studies assessing the impact of certification could be biased if these centers had better outcomes before the start of the program. We determined whether hospitals certified within the first years of the JC program had better outcomes than noncertified hospitals before the start of the certification program.

Methods—

The study sample included Medicare fee-for-service beneficiaries ≥65 years of age discharged with ischemic stroke in 2002 from 5070 hospitals, 317 of which were JC-certified by June 2007. Hierarchical logistic regression and Cox proportional hazards models were used to compare in-hospital mortality, 30-day mortality, and 30-day readmission for patients treated at future JC-certified versus noncertified hospitals.

Results—

Among 366 551 patients, 18% (66 300) were treated at hospitals with centers that were JC-certified within the first few years of the program. These patients were younger, more likely to be white and male, and had fewer comorbidities and hospitalizations within the prior year. Unadjusted in-hospital mortality (4.7% versus 5.5%), 30-day mortality (9.8% versus 11.3%), and readmissions (13.8% versus 14.6%) were lower in the future JC-certified hospitals (all
P
<0.001). These differences remained after risk adjustment (in-hospital mortality: OR, 0.93; 95% CI, 0.90 to 0.96; 30-day mortality: OR, 0.92; 95% CI, 0.87 to 0.96; 30-day readmission: hazard ratio, 0.97; 95% CI, 0.95 to 0.99).

Conclusions—

JC Primary Stroke Center-certified hospitals had better outcomes than noncertified hospitals even before the program began. Cross-sectional studies assessing the effects of stroke center certification need to account for these pre-existing differences.
Infarction in the Territory of Anterior Inferior Cerebellar Artery
Authors: Lee Hyung , Kim Ji Soo , Chung Eun-Ji , Yi Hyon-Ah , Chung In-Sung , Lee Seong-Ryong , Shin Je-Young
Published: September 2009

Background and Purpose—

To define the detailed spectrum of audiovestibular dysfunction in anterior inferior cerebellar artery territory infarction.

Methods—

Over 8.5 years, we prospectively identified 82 consecutive patients with anterior inferior cerebellar artery territory infarction diagnosed by MRI. Each patient completed a standardized audiovestibular questionnaire and underwent a neuro-otologic evaluation, including bithermal caloric tests and pure tone audiogram.

Results—

All but 2 (80 of 82 [98%]) patients had acute prolonged vertigo and vestibular dysfunction of peripheral, central, or combined origin. The most common pattern of audiovestibular dysfunction was the combined loss of auditory and vestibular function (n=49 [60%]). A selective loss of vestibular (n=4 [5%]) or cochlear (n=3 [4%]) function was rarely observed. We could classify anterior inferior cerebellar artery territory infarction into 7 subgroups according to the patterns of neuro-otological presentations: (1) acute prolonged vertigo with audiovestibular loss (n=35); (2) acute prolonged vertigo with audiovestibular loss preceded by an episode(s) of transient vertigo/auditory disturbance within 1 month before the infarction (n=13); (3) acute prolonged vertigo and isolated auditory loss without vestibular loss (n=3); (4) acute prolonged vertigo and isolated vestibular loss without auditory loss (n=4); (5) acute prolonged vertigo but without documented audiovestibular loss (n=24); (6) acute prolonged vertigo and isolated audiovestibular loss without any other neurological symptoms/signs (n=1); and (7) nonvestibular symptoms with normal audiovestibular function (n=2).

Conclusions—

Infarction in the anterior inferior cerebellar artery territory can present with a broad spectrum of audiovestibular dysfunctions. Unlike a viral cause, labyrinthine dysfunction of a vascular cause usually leads to combined loss of both auditory and vestibular functions.
Sensitivity of Salivary Glands to Radiation: from Animal Models to Therapies
Authors: Grundmann O. , Mitchell G.C. , Limesand K.H.
Published: September 2009

Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field.
Lifecourse Socio-economic Mobility and Oral Health in Middle Age
Authors: Pearce M.S. , Thomson W.M. , Walls A.W.G. , Steele J.G.
Published: September 2009

Socio-economic variations in health exist for a wide range of health outcomes, including oral health and oral-health-related quality of life (OHRQoL). Less is known regarding how socio-economic trajectories may influence oral health and OHRQoL. This study examined whether social mobility is related to the number of teeth retained by age 50 years and OHRQoL measured at the same time, using data from the Newcastle Thousand Families Study, a birth cohort established in 1947. Women remaining in the non-manual class had the greatest tooth retention. While promotion of a healthier lifestyle and continued improvements in oral hygiene throughout life appear to be the public health interventions most likely to improve oral health into middle age, there may be sub-groups of the population on which different approaches in terms of public health interventions need to be focused.
Periodontal Therapy Improves Gastric Helicobacter pylori Eradication
Authors: Zarić S. , Bojić B. , Janković Lj. , Dapčević B. , Popović B. , Čakić S. , Milašin J.
Published: September 2009

The oral cavity has been proposed as a reservoir for H. pylori that could be responsible for the refractoriness of gastric infection to triple therapy (antibiotics, antimicrobials, and proton pump inhibitors). The aim of this study was to evaluate the efficiency of combined periodontal and triple therapy vs. triple therapy alone, in gastric H. pylori eradication in persons with H. pylori in the subgingival biofilm. Individuals positive for H. pylori in their gastric and oral samples, as determined by nested PCR, were treated either with periodontal and triple therapy or with triple therapy alone. Our results indicate that 77.3% of those treated with the combined therapy exhibited successful eradication of gastric H. pylori, compared with 47.6% who underwent only triple therapy. Analysis of these data suggests that periodontal treatment in combination with systemic therapy could be a promising approach to increasing the therapy’s efficacy and decreasing the risk of infection recurrence.
Primary Cilia of Odontoblasts: Possible Role in Molar Morphogenesis
Authors: Thivichon-Prince B. , Couble M.L. , Giamarchi A. , Delmas P. , Franco B. , Romio L. , Struys T. , Lambrichts I. , Ressnikoff D. , Magloire H. , Bleicher F.
Published: September 2009

A primary cilium, a sensory organelle present in almost every vertebrate cell, is regularly described in odontoblasts, projecting from the surfaces of the cells. Based on the hypothesis that the primary cilium is crucial both for dentin formation and possibly in tooth pain transmission, we have investigated the expression and localization of the main cilium components and involvement of the OFD1 gene in tooth morphogenesis. Odontoblasts in vitro express tubulin, inversin, rootletin, OFD1, BBS4, BBS6, ALMS1, KIF3A, PC1, and PC2. In vivo, cilia are aligned parallel to the dentin walls, with the top part oriented toward the pulp core. Close relationships between cilium and nerve fibers are evidenced. Calcium channels are concentrated in the vicinity of the basal body. Analysis of these data suggests a putative role of cilia in sensing the microenvironment, probably related to dentin secretion. This hypothesis is enhanced by the huge defects observed on molars from Ofd1 knockout mice, showing undifferentiated dentin-forming cells.
Pharmacokinetics, Safety, and Tolerability of Phentermine in Healthy Participants Receiving Taranabant, a Novel Cannabinoid‐1 Receptor (CB1R) Inverse Agonist
Authors: Addy Carol , Jumes Patricia , Rosko Kimberly , Li Susie , Li Hankun , Maes Andrea , Johnson‐Levonas Amy O. , Chodakewitz Jeffrey , Stoch S. Aubrey , Wagner John A.
Published: September 2009

This study assessed the potential pharmacokinetic interaction and safety/tolerability of taranabant and phentermine coadministration. This was a randomized, double‐blind, 3‐panel, fixed‐sequence study in healthy participants. Panels A, B, and C evaluated the safety/tolerability of phentermine 15 mg coadministered with taranabant 0.5, 1, and 2 mg for 7 days (panel A) and 28 days (panels B and C). In panels A and C, phentermine 15 mg was administered both with (7 days, panel A; 28 days, panel C) and without (7 days) taranabant 0.5 mg or 2 mg to evaluate pharmacokinetics. The primary endpoint was phentermine AUC0–24 hin panels A and C. Secondary endpoints were changes from baseline in blood pressure and heart rate for all panels. The geometric mean ratios and 90% confidence intervals for phentermine AUC0–24 hin the presence/absence of taranabant 0.5 mg and 2 mg were 1.08 (0.99, 1.17) and 1.04 (0.98, 1.10), respectively. No significant differences in blood pressure and heart rate were observed with any treatment versus placebo. Coadministration of taranabant 0.5 mg, 1 mg, and 2 mg with phentermine was well tolerated with no pharmacokinetic interaction and did not result in meaningful changes in blood pressure or heart rate versus placebo.
Anticholinergic Activity of Commonly Prescribed Medications and Neuropsychiatric Adverse Events in Older People
Authors: Nishtala Prasad S. , Fois Romano A. , McLachlan Andrew J. , Bell J. Simon , Kelly Patrick J. , Chen Timothy F.
Published: September 2009

This study sought to determine whether the presence of in vitro anticholinergic activity (AA) among different drugs is associated with reporting of neuropsychiatric adverse events (NPAEs) and whether age affects this relationship. Retrospective case/noncase analyses using Australia's spontaneous Adverse Drug Reaction System (ADRS) database containing 150 475 reports determined crude and adjusted reporting odds ratios (RORs) for NPAEs for 23 drugs with various reported in vitro AA. Covariates were age (treated as a dichotomous variable [≥65 years]), gender, and concomitant use of antipsychotics, benzodiazepines, tricyclic antidepressants, and drugs with recognized inherent anticholinergic properties (anticholinergic drugs). The interaction effect between these covariates and each drug exposure category was examined. Age (≥65 years) has a significant association with greater odds relative to younger age for reporting NPAEs. Drugs with reported significant AA in vitro were not always associated with RORs greater than 1 for reporting NPAEs, highlighting a dissonance between the in vitro AA index and ADRS observations. Significant interactions were observed between age (≥65 years) and exposure to cimetidine, anticholinergic drugs, antipsychotics, and tricyclic antidepressants in modifying odds for reporting NPAEs, reinforcing the need for cautious use and monitoring of drugs with AA in older people.
Comparative Device Assessments
Authors: Ignaut Debra A. , Schwartz Sherwyn L. , Sarwat Samiha , Murphy Heather L.
Published: September 2009

Purpose

The purpose of this study was to compare pen device-naïve patients’ preferences for Humalog® KwikPen™ (insulin lispro injection) (Eli Lilly and Company, Indianapolis, IN) to use of a vial and syringe and FlexPen® (insulin aspart injection) (Novo Nordisk A/S, Bagsvaerd, Denmark).

Methods

This open-label, randomized, crossover 1-day study tested the hypotheses that KwikPen was preferred to vial and syringe, and if this was found to be a significant preference, that KwikPen was preferred to FlexPen. Accuracy of doses prepared, ease of use via insulin device assessment battery, and preference via insulin device preference battery were administered following each pen evaluation, and a final preference question administered following the evaluation of both pens. Clinical measures were not included as subjects injected into an appliance to simulate the injection experience. Primary outcome variables were evaluated by Question 13 of the insulin device preference battery and the final preference question.

Results

Among 232 enrolled patients randomized to 1 of 4 sequences (n = 58), Humalog KwikPen was significantly preferred over vial and syringe and over FlexPen. After patients were asked to assess Humalog KwikPen or FlexPen versus V&S by choosing “strongly agreed” or “agreed” to the following attributes: easy to use, easy to hold in their hands when injecting, and easy to press the injection button, the results exhibited significant differences in patient responses. Humalog KwikPen was significantly more accurate and was preferred to vial and syringe in appearance, quality, discretion, convenience, public use, easy to learn, easy to use, reliability, dose confidence, following insulin regimen, overall satisfaction, and recommendation to others.

Conclusions

Humalog KwikPen was significantly preferred over vial and syringe and FlexPen. When compared with vial and syringe, Humalog KwikPen and FlexPen were easier to use and operate, demonstrated superior accuracy of doses prepared, and preferred by pen-naïve users.
Evaluation of the CSEC Community Intervention Project (CCIP) in Five U.S. Cities
Authors: Ferguson Kristin M. , Soydan Haluk , Lee Sei-Young , Yamanaka Alisa , Freer Adam S. , Xie Bin
Published: September 2009

In response to the commercial sexual exploitation of children (CSEC) within five U.S. cities, the CSEC Community Intervention Project (CCIP) was created to enhance collaboration among nongovernmental organization (NGO) representatives, law enforcement officials and prosecutors in Chicago, Atlantic City, Denver, Washington, D.C., and San Diego. A total of 211 participants were surveyed during a 3-day CCIP training institute held in each city. Evaluation data suggest that participants were positively influenced in their knowledge, skills, and attitudes regarding CSEC. Our findings inform NGO representatives, law enforcement officials, and prosecutors of the importance of professional training and the benefits of cross-disciplinary collaboration in addressing CSEC.
Building to Death: Prisoner Forced Labour in the German War Economy — The Neuengamme Subcamps, 1942—1945
Authors: Buggeln Marc
Published: September 2009

In 1944 most concentration camp prisoners were not interned in the main camps but in subcamps. These subcamps were erected near important armament production sites, where the work power of the prisoners was needed. The conditions in these subcamps were sometimes even more terrible than in the main camps. In historiography, the phrase ‘extermination through work’ is often used in order to describe the subcamps. However, newer studies show that conditions differed enormously between camps. For this reason it is necessary to compare the conditions in the different subcamps systematically. My article discusses the reasons for the differences that have been put forward so far. Afterwards I show that an exploration of the subcamps of Neuengamme leads to somewhat different results, and I argue that, therefore, the phrase ‘extermination through work’ should be used more cautiously.
Implicit media frames: Automated analysis of public debate on artificial sweeteners
Authors: Hellsten Iina , Dawson James , Leydesdorff Loet
Published: September 2009

The framing of issues in the mass media plays a crucial role in the public understanding of science and technology. This article contributes to research concerned with the analysis of media frames over time by making an analytical distinction between implicit and explicit media frames, and by introducing an automated method for the analysis of implicit frames. In particular, we apply a semantic maps method to a case study on the newspaper debate about artificial sweeteners, published in the New York Times between 1980 and 2006. Our results show that the analysis of semantic changes enables us to filter out the dynamics of implicit frames, and to detect emerging metaphors in public debates. Theoretically, we discuss the relation between implicit frames in public debates and the codification of meaning and information in scientific discourses, and suggest further avenues for research interested in the automated analysis of frame changes and trends in public debates.
Patient Satisfaction of Young Adults in Rural Clinics
Authors: Lemley Kathryn B. , Marks Beth
Published: September 2009

In an effort to increase primary care services to Medicare and Medicaid patients, the Rural Health Clinics Services Act of 1977 required collaborative practices to include mid-level providers such as nurse practitioners (NPs). As a result, NPs have increased access to primary care in many rural and underserved areas. Now, in an effort to improve quality of health care, the Centers for Medicare and Medicaid Services (CMS) initiated public reporting of health care quality indicators. Although patient satisfaction is recognized as a quality indicator, few researchers have investigated patient satisfaction with NPs in rural family practice. A patient satisfaction survey (PSS) was distributed to a convenience sample of 213 young adult patients seen by five nurse practitioners in two rural family practice clinics. Survey results are analyzed and discussed within the framework of current CMS policy initiatives such as performance measures, pay for performance (P4P), transparency, and public reporting.
U.S. Health Reform
Authors: Keepnews David M.
Published: September 2009

A new political climate in the United States has raised renewed hope for achieving much needed reform of the U.S. health care system. Opposition to reform raises old arguments, however, including warnings against “big government,” currently focused on proposals to include a public plan option in health reform. But greater government involvement in health care is needed to achieve comprehensive reform. Further substantial delay in achieving reform is unthinkable; success will require continued and expanded support efforts. Although a strong public plan option would represent a significant step forward, continued advocacy by proponents of single-payer health care can help strengthen broader efforts to achieve public accountability. Supporters of meaningful health reform will need to continue their efforts long past the passage of reform legislation.
The transcription factors STAT5A/B regulate GM-CSF–mediated granulopoiesis
Authors: Kimura Akiko , Rieger Michael A. , Simone James M. , Chen Weiping , Wickre Mark C. , Zhu Bing-Mei , Hoppe Philipp S. , O'Shea John J. , Schroeder Timm , Hennighausen Lothar
Published: September 2009

Neutrophils play a vital role in the immune defense, which is evident by the severity of neutropenia causing life-threatening infections. Granulocyte macrophage-colony stimulating factor (GM-CSF) controls homeostatic and emergency development of granulocytes. However, little is known about the contribution of the downstream mediating transcription factors signal transducer and activator of transcription 5A and 5B (STAT5A/B). To elucidate the function of this pathway, we generated mice with complete deletion of both Stat5a/b genes in hematopoietic cells. In homeostasis, peripheral neutrophils were markedly decreased in these animals. Moreover, during emergency situations, such as myelosuppression, Stat5a/b-mutant mice failed to produce enhanced levels of neutrophils and were unable to respond to GM-CSF. Both the GM-CSF–permitted survival of mature neutrophils and the generation of granulocytes from granulocyte-macrophage progenitors (GMPs) were markedly reduced in Stat5a/b mutants. GMPs showed impaired colony-formation ability with reduced number and size of colonies on GM-CSF stimulation. Moreover, continuous cell fate analyses by time-lapse microscopy and single cell tracking revealed that Stat5a/b-null GMPs showed both delayed cell-cycle progression and increased cell death. Finally, transcriptome analysis indicated that STAT5A/B directs GM-CSF signaling through the regulation of proliferation and survival genes.
Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study
Authors: Stolz D. , Smyrnios N. , Eggimann P. , Pargger H. , Thakkar N. , Siegemund M. , Marsch S. , Azzola A. , Rakic J. , Mueller B. , Tamm M.
Published: September 2009

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy.

In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis.

Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2–21) daysversus9.5 (1.5–17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02–2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar.

Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.
Association between Gc genotype and susceptibility to TB is dependent on vitamin D status
Authors: Martineau A. R. , Leandro A. C. C. S. , Anderson S. T. , Newton S. M. , Wilkinson K. A. , Nicol M. P. , Pienaar S. M. , Skolimowska K. H. , Rocha M. A. , Rolla V. C. , Levin M. , Davidson R. N. , Bremner S. A. , Griffiths C. J. , Eley B. S. , Bonecini-Almeida M. G. , Wilkinson R. J.
Published: September 2009

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB).

The following subjects were recruited into case–control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between casesversuscontrols. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-γ release assays were also performed on 36 Gujarati Asian TB contacts.

The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19–6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol·L−1(p = 0.01) but not if serum 25(OH)D was ≥20 nmol·L−1(p = 0.36).

Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-γ release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.
Statins inhibit matrix metalloproteinase release from human lung fibroblasts
Authors: Kamio K. , Liu X. D. , Sugiura H. , Togo S. , Kawasaki S. , Wang X. , Ahn Y. , Hogaboam C. , Rennard S. I.
Published: September 2009

Pleiotropic effects of statins have been reported to include inhibition of matrix metalloproteinase (MMP) release from macrophages and endothelial cells. We evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodelling processes.

Monolayer and three-dimensional (3D) collagen gel cultures of fibroblasts were used. Cytokines (tumour necrosis factor-α and interleukin-1α) were used to induce MMP release and mRNA expression. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Atorvastatin inhibited MMP-1 and -3 release and mRNA expression in both culture systems. Similar results were obtained with simvastatin and fluvastatin.

In 3D cultures where cytokines also stimulated MMP-9 release, atorvastatin also inhibited MMP-9 release. In 3D cultures, cytokines together with NE induced collagen degradation, which was also inhibited by atorvastatin. The effect of atorvastatin was reversed by mevalonate and geranylgeranyl-pyrophosphate but not by farnesyl-pyrophosphate.

The current data suggest that statins may modulate remodelling processes mediated by fibroblasts by inhibiting MMP release.