bluuebunny/crossref_metadata_2025 huggingface dataset:
Choosing a Right Surfactant for Respiratory Distress Syndrome Treatment
Authors: Ramanathan Rangasamy
Published: October 2008

Respiratory distress syndrome (RDS) is the most common cause of respiratory insufficiency in preterm infants, especially those born at <30 weeks of gestation. Continuous positive airway pressure has been used since the 1970s as a primary mode of treatment for RDS. Surfactant therapy became available in the 1980s and has become the standard care for infants with or at risk for RDS. Surfactant therapy has been shown to decrease air leaks, neonatal and infant mortality as well as cost among survivors. Natural surfactants derived from animal sources containing surfactant proteins B (SP-B) and C (SP-C) as well as synthetic surfactants with functional SP-B- or SP-C-like protein mimics have been extensively evaluated in preterm neonates with or at risk for RDS. Evidence from randomized controlled trials indicates that treatment with natural surfactants results in faster weaning of supplemental oxygen and mean airway pressure, decreased duration of mechanical ventilation, and decreased mortality when compared to synthetic surfactants. Furthermore, at the present time, there are no approved synthetic surfactants available for use in preterm infants. Beractant, calfactant and poractant alfa are the three commonly used natural surfactants worldwide. Comparative studies including prospective randomized trials as well as large retrospective studies have shown significant differences in outcome and cost among these three natural surfactants. Of the eight prospective, randomized controlled trials and two retrospective studies involving the natural surfactant preparations, treatment with poractant alfa resulted in a significantly decreased mortality, decreased need for additional doses, faster weaning of oxygen and reduced hospital costs when compared to treatment with beractant or calfactant. These differences in outcome may be due to differences in phospholipid and SP-B content, amount of antioxidant phospholipids, plasmalogens, anti-inflammatory properties and viscosity among these three surfactants. Additional studies of administering surfactant non-invasively via laryngeal mask airway in preterm infants weighing >1,200 g and as an aerosol preparation are currently in progress.
Outcomes of Multiplets
Authors: Shinwell E.S. , Haklai T. , Eventov-Friedman S.
Published: October 2008

Outcomes, both short and long term, differ between singletons and multiplets. Recently, a number of large, well-designed studies have clarified these differences, particularly in light of major changes in perinatal and neonatal care that have influenced changing outcomes. Accordingly, this article will review risks for singletons, twins and higher-order multiples as whole groups and also after correction for gestational age and other potential confounding variables that differ markedly between the groups. In addition, we will focus on the effects of certain factors such as antenatal steroid therapy and gender. Finally, we will detail the specific long-term risks for multiples in terms of growth and neurodevelopmental disabilities.
Severe Congenital Myasthenia Gravis of the Presynaptic Type with Choline Acetyltransferase Mutation in a Chinese Infant with Respiratory Failure
Authors: Yeung Wai L. , Lam Ching W. , Fung Lai W.E. , Hon Kam L.E. , Ng Pak C.
Published: October 2008

We report a severe case of congenital myasthenia gravis in a Chinese newborn who presented with complete ptosis, severe hypotonia, dysphagia and respiratory insufficiency with recurrent apnea that required mechanical ventilatory support since birth. Routine neurophysiologic studies, including the 3-Hz repetitive stimulation test and electromyogram were normal. Neostigmine and edrophonium tests were also negative. However, decremental response to 3-Hz stimulation became apparent after depleting the muscles with trains of 10-Hz stimuli for 10 min. The infant was subsequently confirmed to have heterozygous mutations in the choline acetyltransferase genes, p.T553N and p.S704P. Both missense mutations are novel mutations. The child remained on positive pressure ventilation at 3 years of age despite treatment with high-dose anticholinesterase. This case highlights the difficulty of making an early diagnosis based on clinical presentation and routine electrophysiologic tests, especially when neonatologists are not familiar with this condition. Further, as there are different genetic defects causing different types of congenital myasthenia gravis, anticholinesterase therapy may be beneficial to some but detrimental to others. Therefore, the exact molecular diagnosis is an important guide to therapy. A high index of suspicion coupled with extended electrodiagnostic tests in clinically suspected patients will ensure the selection of appropriate genetic molecular study for confirming the diagnosis.
Collagen/Endogenous Thrombin-Induced Platelet Aggregation in Cord versus Adult Whole Blood
Authors: Cvirn Gerhard , Kutschera Joerg , Wagner Thomas , Ferstl Ulrika , Vrecko Karoline , Hallstrom Seth , Juergens Guenther , Koestenberger Martin
Published: October 2008

Background: In previous studies, neonatal platelets have been shown to be hypoaggregable to various agonists when compared with adult platelets. Objectives: It was the aim of this study to investigate the aggregability of neonatal versus adult platelets when the physiological relevant agonist collagen/endogenous thrombin is used. Methods and Results: Whole blood (WB) aggregation experiments employing the impedance method revealed the same responsiveness of neonatal and adult platelets to collagen/endogenous thrombin. Maximum aggregation (13.5 ± 3.2 vs. 13.6 ± 3.2 Ω; p = 0.94), slope (5.8 ± 1.8 vs. 6.2 ± 2.6 Ω/min; p = 0.79) and lag time until the onset of platelet aggregation (38.7 ± 8.9 vs. 42.6 ± 16.5 s; p = 0.59) were similar in cord and adult WB. However, the rise in serotonin plasma levels due to platelet activation was significantly lower in neonates versus adults (227.57 ± 57.65 vs. 473.34 ± 155.75 ng/ml; p = 0.0001). Furthermore, we found a fast capability of cord plasma to generate (the efficient platelet agonist) endogenous thrombin: thrombin generation started significantly earlier in cord compared with adult plasma (215 ± 19 vs. 247 ± 21 s; p = 0.01). Moreover, thrombelastometry revealed significantly shorter coagulation times in cord versus adult WB activated with collagen/endogenous thrombin (229.8 ± 12.5 vs. 256.3 ± 25.3 s; p = 0.003). Conclusions: The efficient platelet aggregation in cord WB provoked by collagen/endogenous thrombin might help to explain the clinically observed well-functioning primary hemostasis of neonates.
Single Nucleotide Polymorphisms Associated with Coronary Heart Disease Predict Incident Ischemic Stroke in the Atherosclerosis Risk in Communities Study
Authors: Morrison Alanna C. , Bare Lance A. , Luke May M. , Pankow James S. , Mosley Thomas H. , Devlin James J. , Willerson James T. , Boerwinkle Eric
Published: October 2008

Ischemic stroke and coronary heart disease (CHD) may share genetic factors contributing to a common etiology. This study investigates whether 51 single nucleotide polymorphisms (SNPs) associated with CHD in multiple antecedent studies are associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. From the multiethnic ARIC cohort of 14,215 individuals, 495 validated ischemic strokes were identified. Cox proportional hazards models, adjusted for age and gender, identified three SNPs in Whites and two SNPs in Blacks associated with incident stroke (p ≤ 0.05). The rs11628722 polymorphism in SERPINA9 was associated with incident stroke in Whites and Blacks, even after taking into account traditional risk factors. The idea that ischemic stroke and CHD may share some common genetic factors, such as variation in SERPINA9, should be investigated in other studies.
Polymorphisms of Homocysteine Metabolism Are Associated with Intracranial Aneurysms
Authors: Semmler Alexander , Linnebank Michael , Krex Dietmar , Götz Anika , Moskau Susanna , Ziegler Andreas , Simon Matthias
Published: October 2008

Background: Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms. Methods: Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genotyped for the following polymorphisms: methionine synthase (MTR) c.2756A→G, methylenetetrahydrofolate reductase (MTHFR) c.677C→T, MTHFR c.1298A→C, cystathionine β-synthase (CBS) c.844_855ins68, CBS c.833T→C, dihydrofolate reductase (DHFR) c.594 + 59del19bp, glutathione S-transferase Ω-1 (GSTO1) c.428C→A, reduced folate carrier 1 (RFC1) c.80G→A and transcobalamin 2 (Tc2) c.776C→G. Results: The G-allele of the missense polymorphism Tc2 c.777C→G was found to be underrepresented in patients, suggesting that this variant may protect from the formation of cerebral aneurysms [odds ratio per two risk alleles (OR) 0.48; 95% confidence interval (CI) 0.30–0.77; p = 0.002]. We obtained borderline results for the G-allele of RFC1 c.80G→A (OR 1.64; 95% CI 1.01–2.65; p = 0.051) and the insertion allele of DHFR c.594 + 59del19bp (OR 1.61; 95% CI 1.00–2.60; p = 0.059), which were found to be overrepresented in patients. Conclusion: Polymorphisms of homocysteine metabolism are possible risk factors for the formation of intracranial aneurysms.
History of Neonatal Resuscitation – Part 3: Endotracheal Intubation
Authors: Obladen Michael
Published: October 2008

Endotracheal intubation to resuscitate neonates was used by Scheel in 1798. A century before endotracheal anesthesia was developed, inventive obstetricians constructed devices for endotracheal intubation of infants and mastered their insertion, localization, and airtight sealing. Fell’s laryngoscope, Magill’s intubation forceps and tissue-friendly materials were significant contributions of the 20th century to endotracheal intubation of the newborn. The striking absence of scientific studies on the most efficient resuscitation techniques for neonates can be explained by the difficulty to adjust for the personal skills of the resuscitator.
Anti-IgE for the Treatment of Allergic Rhinitis – and Eventually Nasal Polyps?
Authors: Verbruggen Katia , Van Cauwenberge Paul , Bachert Claus
Published: October 2008

In allergic rhinitis, cross-linking of IgE molecules upon allergen contact induces degranulation of mast cells and basophils within the mucosal tissue and results in the release of typical mediators, which consecutively induce the well-known symptoms. Omalizumab counteracts these interactions by reducing serum levels of free IgE. Therapy targeted at IgE also interferes with its binding to the low-affinity receptors inhibiting the amplification of the Th2-type response. Treatment of allergic rhinitis with anti-IgE has been shown to be safe and to reduce specific symptoms. Furthermore, the combination of omalizumab with specific immunotherapy may not only increase efficacy but also safety in selected patients. Therefore, we reviewed previously published studies on omalizumab therapy in allergic rhinitis, either as monotherapy or in combination with immunotherapy. In patients with nasal polyps, a local multiclonal IgE response has recently been described, initiated by Staphylococcus aureus-derived enterotoxins, which at least modifies the inflammatory reaction within the tissue. Evidence accumulates that these enterotoxins act as superantigens resulting in a multiclonal T- and B-cell activation with massive IgE formation within the airways. Because of the multiclonality, a range of allergens could possibly maintain a constant degranulation of mast cells present in the polyp tissue, which may contribute to disease severity. We here discuss a proof-of-concept treatment trial with omalizumab in nasal polyposis, which – in case of a positive therapeutic response – would also pave the way for anti-IgE treatment approaches for severe non-atopic lower airway disease.
Expression and Characterization of PGD2 Receptors in Chronic Rhinosinusitis: Modulation of DP and CRTH2 by PGD2
Authors: Yamamoto Miki , Okano Mitsuhiro , Fujiwara Tazuko , Kariya Shin , Higaki Takaya , Nagatsuka Hitoshi , Tsujigiwa Hidetsugu , Yamada Masao , Yoshino Tadashi , Urade Yoshihiro , Nishizaki Kazunori
Published: October 2008

Background: Prostaglandin D2 (PGD2) participates in airway inflammation. We reported that levels of hematopoietic-type PGD2 synthase (h-PGDS) in sinonasal tissues may play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Two PGD2 receptors have been isolated, DP and CRTH2, but whether they participate in CRS remains unclear. We sought to determine the expression and characterization of DP and CRTH2 in CRS. Methods: Expression of DP and CRTH2 in nasal polyps (NP) and uncinate process mucosae (UPM) was examined by in situ hybridization and immunohistochemistry and evaluated by real-time quantitative PCR. h-PGDS, IL-5, eotaxin and RANTES expression was also determined. In addition, the effect of PGD2 on the expression of both receptors in UPM was assessed. Results: DP was widely expressed, not only in infiltrating inflammatory cells but also in constitutive cells such as vascular endothelial cells and ciliated columnar epithelia. CRTH2 was selectively expressed in inflammatory cells and some glands. Significantly greater levels of DP mRNA and conversely decreased levels of CRTH2 mRNA were observed in NP compared with UPM. DP and CRTH2 mRNA levels were not only positively and inversely correlated with levels of h-PGDS but also with eotaxin, respectively. Furthermore, addition of PGD2 significantly increased DP expression and conversely reduced CRTH2 expression in UPM. Conclusions: These results suggest that distinct expression of DP and CRTH2 is associated with the pathophysiology of CRS, including NP formation, and the expression of these receptors may be regulated by h-PGDS and PGD2.
Bronchial Diffusing Capacity of Nitric Oxide Is Increased in Patients with Allergic Rhinitis
Authors: Mäkinen Tarja , Lehtimäki Lauri , Kinnunen Hannele , Nieminen Riina , Kankaanranta Hannu , Moilanen Eeva
Published: October 2008

Background: Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates allows calculation of flow-independent NO parameters: alveolar NO concentration, bronchial NO flux, bronchial diffusing capacity of NO and bronchial wall NO concentration. Methods: In the present study, we measured the flow-independent NO parameters and inflammatory markers in exhaled breath condensate (EBC) and in serum in 14 patients with seasonal allergic rhinitis (AR) without asthma, and in 14 age- and sex-matched healthy volunteers. Results: At symptomatic stage before the treatment, patients with AR had higher bronchial wall diffusing capacity of NO than healthy volunteers (p = 0.024), but there were no differences in bronchial wall NO concentration or alveolar NO concentration. Patients with AR had also increased 8-isoprostane levels in the EBC (p = 0.040), and increased serum levels of IgE (p = 0.002) and eosinophil cationic protein (ECP; p = 0.027). Two-week treatment with nasal glucocorticoid mometasone decreased symptom scores and serum ECP levels but had no effect on NO parameters or 8-isoprostane levels in EBC. Conclusions: Noninvasive markers of airway inflammation showed subclinical lower airway inflammation in patients with AR without asthma, but short-term treatment with nasal glucocorticoids did not affect most of the markers of lower airway inflammation.
Sex Differences in Stroke
Authors: Turtzo L. Christine , McCullough Louise D.
Published: October 2008

Increasing evidence suggests that sex differences exist in the etiology, presentation, treatment, and outcome from stroke. The reasons for these sex disparities are becoming increasingly explored, but large gaps still exist in our knowledge. Experimental studies over the past several years have demonstrated intrinsic sex differences both in vivo and in animal models which may have relevance to our understanding of stroke in clinical populations. A greater understanding of the differences and similarities between males and females with respect to the risk factors, pathophysiology, and response to stroke will facilitate the design of future clinical trials and enhance the development of treatment strategies to improve stroke care in both sexes. This article reviews the current literature on sex differences in stroke with an emphasis on the clinical data, incorporating an analysis of bench research as it pertains to the bedside.
Economic Evaluation alongside a Phase II, Multi-Centre, Randomised Controlled Trial of Very Early Rehabilitation after Stroke (AVERT)
Authors: Tay-Teo K. , Moodie M. , Bernhardt J. , Thrift A.G. , Collier J. , Donnan G. , Dewey H.
Published: October 2008

Background/Purpose: The effectiveness and costs of very early rehabilitation after stroke are unknown. This study assessed the cost effectiveness of very early mobilisation in addition to standard care (VEM) compared with standard care alone (SC). Methods: Cost-effectiveness analysis alongside a phase II, multi-centre, randomised controlled trial (RCT) with blinded outcome assessments. Less than 24 h after stroke, patients were recruited from two stroke units and randomised to receive VEM or SC. The intervention continued until discharge or 14 days, whichever was sooner. The efficacy measure was a dichotomised modified Rankin Scale (mRS) at 3 months with mRS ≤2 representing good outcome. Costs were determined from medical records and patient interviews at 3, 6 and 12 months. National average (where available) or local costs were applied for the reference year 2004. Differences in mean total costs at 3 and 12 months were tested using t test assuming unequal variances. An incremental cost-effectiveness ratio was calculated and probabilistic uncertainty analysis was undertaken. Results: The sample consisted of 38 VEM and 33 SC patients. A trend for good outcome with VEM compared to SC was found (adjusted OR 4.10, 95% CI 0.99–16.88, p = 0.051). Patients receiving VEM incurred significantly less costs at 3 months (AUD 13,559) compared with SC (AUD 21,860; p = 0.02). This difference in mean per patient total cost persisted at the 12-month assessment (VEM: AUD 17,564; SC: AUD 29,750; p = 0.03). VEM was found to be a ‘dominant’ (more effective, less cost) intervention when compared to SC at 3 months. Conclusion: These findings provide preliminary evidence that VEM is likely to be cost-effective. A large RCT is currently underway to confirm the cost effectiveness of VEM.
Predictors of Carotid Clamping Intolerance during Endarterectomy That Would Be Wise to Apply to Stenting Procedures
Authors: Anzola G.P. , Limoni P. , Cavrini G.
Published: October 2008

Background and Purpose: Carotid artery stenting procedures are increasingly being performed with devices such as the MO.MA or the Parodi system that involve endovascular clamping of the common carotid artery, thus exposing the ipsilateral hemisphere to the risk of hypoperfusion. The aim of the present study was to look for predictors of carotid clamping intolerance by means of transcranial Doppler. Patients and Methods: We analysed the findings of an earlier Italian multicentre prospective study (SCITEA, Italian Cooperative Study of Transcranial Doppler in Carotid Endarterectomy) in which 513 consecutive patients (males/females 397/116, mean age 67 ± 7 years, mean carotid stenosis 81 ± 11%, NASCET method) scheduled to undergo carotid endarterectomy had been investigated non-invasively with transcranial Doppler, and we correlated the data obtained preoperatively with the need to insert a shunt during surgery as an index of intolerance to carotid clamping. Results: Four hundred and thirty-nine patients (85.6%) underwent surgery without and 74 (14.4%) with the insertion of a shunt. Patients who needed a shunt (intolerant) had a significantly higher decrement in mean flow velocity in the ipsilateral middle cerebral artery (MCA) after compression of the ipsilateral common carotid artery (71.8 ± 22 vs. 30.6 ± 24%) and were significantly more likely to have non-recruitable collateral pathways (75 vs. 18%). Logistic regression analysis confirmed that an MCA decrement of >85% (p = 0.005) and no potential collateralization (p = 0.011) were independent predictors of clamping intolerance. Combining the results of both compression tests (MCA decrement and collateral recruitment) yielded a sensitivity of 64%, a specificity of 99%, a positive predicted value of 88%, a negative predicted value of 95% and an overall accuracy of 95% in predicting shunt insertion. Conclusions: The preoperative assessment of recruitable collaterals and of maximal decrement in MCA mean flow velocity after carotid compression are useful predictors of carotid clamping intolerance. The criteria derived from carotid endarterectomy need to be applied and validated in a prospective series of patients undergoing carotid artery stenting procedures.
Alpha-Synuclein mRNA Levels Correspond to Beck Depression Inventory Scores in Females with Eating Disorders
Authors: Frieling Helge , Gozner Andreas , Römer Konstanze D. , Wilhelm Julia , Hillemacher Thomas , Kornhuber Johannes , de Zwaan Martina , Jacoby Georg E. , Bleich Stefan
Published: October 2008

α-Synuclein (α-Syn) is a neuronal protein involved in the regulation of brain serotonin and dopamine levels. We analyzed the peripheral expression of α-Syn mRNA and Beck Depression Inventory scores in female patients suffering from anorexia nervosa (n = 18) or bulimia nervosa (n = 24). We found a significant positive association between α-Syn mRNA expression and the total scores of the Beck Depression Inventory (linear regression; R2 = 0.20; p = 0.003). α-Syn may play a pathophysiological role in depressive symptoms associated with eating disorders. Further investigations in patients with depression as a sole diagnosis are needed to support its role in the pathogenesis of major depression.
Decline of Serum HBV DNA and No Change Apportioned by the Same Hepatic Parenchyma Cell Volume from Hepatic Fibrosis Stage 1 to Stage 4 during the Natural History of Chronic Hepatitis B
Authors: Ke Wei-Min , Xie Shi-Bin , Yu Li-Na , Liu Ting , Lai Jing , He Da-Qiu , Li Xiao-He , Gao Zhi-Liang , Ke Ying , Chen Pei-Jia
Published: October 2008

During the initial phase of chronic hepatitis B virus (HBV) infection, serum HBV DNA levels are high. Contrarily, fibrosis, cirrhosis and hepatocellular carcinoma have been found in patients with lower serum HBV DNA levels. The aim of this study is to clarify HBV DNA level dynamics of serum apportioned by the same hepatic parenchyma cell volume (HPCV) in hepatic fibrosis stages 1–4 during the natural history of chronic hepatitis B. Serum HBV DNA levels were evaluated by real-time polymerase chain reaction. Further, serum HBV DNA levels were apportioned by and compared with the same HPCV in hepatic fibrosis stages 1–4, respectively. Serum HBV DNA levels were 8.91 × 106 ± 4.37 × 101, 8.13 × 106 ± 7.41 × 101, 9.55 × 105 ± 1.02 × 102, and 4.07 × 105 ± 7.24 × 101 copies/ml, respectively; there were differences among hepatic fibrosis stages 1–4 (p < 0.021–0.000). However, serum HBV DNA levels apportioned by the same volume of hepatic parenchyma cells in hepatic fibrosis stages 1–4 were 3.47 × 1010 ± 8.71 × 102, 1.02 × 1011 ± 9.55 × 102, 1.41 × 1010 ± 2.57 × 103, and 3.72 × 1010 ± 3.02 × 103 with HPCV proportions 65.9, 62.7, 58.9, and 53.3%, respectively; there were no differences among hepatic fibrosis stages 1–4 (p > 0.203–0.967).Following the progression of hepatic fibrosis from stage 1 to 4, ongoing decline of HPCV is responsible for a declining trend of serum HBV DNA levels.
Electroporation at Low Voltages Enables DNA Vaccine to Provide Protection against a Lethal H5N1 Avian Influenza Virus Challenge in Mice
Authors: Zhou Yu , Fang Fang , Chen Jianjun , Wang Huadong , Chang Haiyan , Yang Zhongdong , Chen Ze
Published: October 2008

Objective: Electroporation has been proved to enhance the efficacy of intramuscular delivery of DNA. However, the process of electroporation causes pain and discomfort to the patient receiving the treatment. Higher the electroporation voltages inflict greater pain, and this limits the circumstances in which the technique can be used clinically. The voltages generally used for electroporation in animals range from 100 to 1,200 V/cm. We studied the effect of DNA vaccination when electroporation was performed at lower voltages. Methods: BALB/c mice were immunized twice by electroporation, at a 3-week interval, with H5N1 virus hemagglutinin (HA) DNA. One week after the booster had been given, the mice were challenged with a lethal dose of mouse-adapted H5N1 virus. The immune effects of HA DNA were evaluated by the survival rate, lung virus titer, bodyweight change and antibody titer of the mice. Results: The higher the voltage used, the more able were the mice to survive the challenge. However, a significant degree of protection could also be achieved with a voltage as low as 5 V. When electroporation was performed at a voltage of 10 V, an immunization amount of 5 µg is enough for HA DNA to provide effective protection. Conclusion: Low-voltage electroporation can induce immunity and protect mice effectively. There is, therefore, the potential to reduce the voltages currently used for DNA electroporation.
Effect of Exercise on Cardiac Tissue Oxidative and Inflammatory Mediators in Chronic Kidney Disease
Authors: Bai Y. , Sigala W. , Adams G.R. , Vaziri N.D.
Published: October 2008

Background: Chronic renal failure (CRF) results in diminished physical activity and increased risk of cardiovascular disease (CVD). CVD risk factors are raised by sedentary life style and ameliorated by physical fitness in the general population. Accordingly, exercise improves hypertension, endothelial dysfunction, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-risk populations. This study was designed to explore the effect of exercise on oxidative and inflammatory mediators in the left ventricle (LV) of CRF rats. Methods and Results: One week after 5/6 nephrectomy female rats were housed in either regular cages or cages equipped with running wheels for 4 weeks. Sham-operated rats housed in regular cages served as controls. Sedentary CRF rats exhibited azotemia, hypertension, anemia, oxidative stress, activation of NF-κB and upregulations of reactive oxygen species-generating enzyme, NAD(P)H oxidase, MCP-1, cyclooxygenase-2 (COX-2), and PAI-1 in LV. The CRF rats assigned to the exercise group ran 6.8 ± 0.7 km/day and 72 ± 8 min/day. Voluntary exercise reversed NF-κB activation and lowered NAD(P)H oxidase, PAI-1, MCP-1 and COX-2 abundance, increased LV mass by raising myofibrillar proteins and ameliorated anemia without affecting renal function or arterial pressure. Conclusions: CRF resulted in upregulation of prooxidant/proinflammatory pathways in LV. These changes were ameliorated by exercise, which indicates the potential cardiovascular benefit of exercise in renal insufficiency.
Effects of Glucose Deprivation or Glucose Instability on Mesangial Cells in Culture
Authors: de Lima e Santos Carla , Arnoni Carine P. , Schor Nestor , Boim Mirian A.
Published: October 2008

Mesangial cell (MC) abnormalities play a central role in diabetic nephropathy. Variations in plasma glucose levels may contribute to MC dysfunction. This study evaluated the effects of glucose deprivation or fluctuations on MC viability, glucose uptake, and mesangial matrix production. The expression levels of fibronectin and glucose transporters (GLUT-1 and GLUT-4) were determined. MCs were exposed to normal (NG, 10 mM), low (LG, 1 mM) or high (HG, 30 mM) glucose concentrations for 1, 4, 12, 24 and 72 h. Glucose oscillation was achieved by alternating the glucose concentration (LG, NG or HG) in the medium every 8, 12, and 4 h over a total of 24 h. LG induced a significant increase (90%) in glucose uptake dependent of GLUT-1, which was not followed by alteration in fibronectin expression. Fluctuations in glucose levels induced a rise in glucose uptake also mediated by GLUT-1. Fibronectin did not change in any oscillation group. Results suggest that, in spite of a rise in glucose uptake by MCs under low glucose availability, or exposed to glucose fluctuations, mesangial matrix overproduction did not occur. Thus, neither glucose deprivation nor glucose instability, at least during short periods, is involved in the mesangial matrix overproduction observed in diabetes.
Familiality of Cardiovascular Mortality in End-Stage Renal Disease Patients
Authors: Naiman Natalie , Cheung Alfred K. , Goldfarb-Rumyantzev Alexander S.
Published: October 2008

A very high rate of cardiovascular (CV) death is well recognized in individuals with end-stage renal disease (ESRD). Besides many other factors, this excess risk may also be related to familiality. We tested this hypothesis by estimating the risk of CV death among both ESRD patients and their relatives. In this case-control study, we used the Utah Population Database (UPDB), which includes genealogy records, state-wide death certificates as well as other data sets. These have been linked to the University of Utah Health Sciences Enterprise Data Warehouse which provides multiple diagnosis data sources. Patients with ESRD either on dialysis or who received a kidney transplant were identified in the clinical databases at the University of Utah Dialysis Program and Kidney Transplant Program or from Utah death certificates. CV deaths were identified by the reporting on the death certificates. The relative risks for CV death, adjusted for several potential confounders in the ESRD patients (n = 516) and in their first-degree (n = 2,418) and second-degree (n = 7,720) relatives were estimated in relation to the general population. Using information from death certificates, ESRD patients were found to have disproportionately increased risk for CV mortality (relative risk or RR = 2.4; 95% CI 2.11–2.72), compared to the general population. First-degree relatives of ESRD patients were also found to have an increased CV mortality risk (RR = 1.10; 95% CI 1.01–1.20). When the specific categories of CVD were analyzed, the first-degree relatives also had higher risks for death from acute myocardial infarction (RR = 1.20; 95% CI 1.03–1.40) or heart failure (RR = 1.32; 95% CI 1.12–1.56). An increased risk for CV mortality was, however, not observed in second-degree relatives of ESRD patients, except for the subcategory of hypertensive heart disease (RR = 1.24, 95% CI 1.01–1.49). In conclusion, this study suggests that, in addition to many putative risk factors, the increased risk of CV death in ESRD patients may have a familial contribution.
Effects of Long-Term Cholecalciferol Supplementation on Mineral Metabolism and Calciotropic Hormones in Chronic Kidney Disease
Authors: Okša Adrián , Spustová Viera , Krivošíková Zora , Gazdíková Katarína , Fedelešová Viera , Lajdová Ingrid , Štefíková Kornélia , Bernasovská Gabriela , Žilinská Zuzana , Dzúrik Rastislav
Published: October 2008

Background: Data on the efficacy and safety of long-term vitamin D supplementation in chronic kidney disease (CKD) are scarce. We assessed the effects of the 12-month vitamin D3 treatment on mineral metabolism and calciotropic hormones in patients with CKD stages 2–4. Methods: Eighty-seven patients (mean age 66 years, men/women 33/54) were randomized to cholecalciferol treatment with either 5,000 or 20,000 IU/week. Serum calcium, phosphate, 25(OH)D3, 1,25(OH)2D3, PTH and urinary mineral concentrations were obtained at baseline and after 4, 8 and 12 months. Results: The median serum mineral concentrations were normal and not changed throughout the study. The number of hypercalciuric patients slightly increased with higher dose, but no sustained rise in calciuria was present. Vitamin D insufficiency/deficiency was revealed in 72 (83%) patients at baseline and 37 (43%) at month 12. The 25(OH)D3 levels increased more with higher dose; a rise in 1,25(OH)2D3 was less impressive. The parathyroid hormone (PTH) concentrations were reduced, but the number of subjects with PTH below the lower limit for CKD stage 3 increased equally with both doses. Conclusions: Vitamin D insufficiency/deficiency in CKD significantly improved after the 12-month cholecalciferol treatment, with higher dose being more effective and equally safe. Further studies of vitamin D3 effects on bone metabolism are warranted.
Organization of Projection-Specific Interneurons in the Spinal Cord of the Red-Eared Turtle
Authors: Nissen Ulla Vig , Moldovan Mihai , Hounsgaard Jørn , Glover Joel C.
Published: October 2008

Using differential retrograde axonal tracing, we identified motoneurons (MNs) and projection-specific interneuron (IN) classes in lumbar segment D9 of the adult red-eared turtle spinal cord. We characterized the distribution of these neurons in the transverse plane, and estimated their numbers and proportions. Different labeling paradigms allowed us to distinguish ipsilateral INs (IINs) from commissural INs (CINs), and to identify IINs and CINs with either ascending (a) axons, descending (d) axons, or axons that bifurcate to both ascend and descend (ad). Local interneurons with axons shorter than 1 segment in length were not studied. We show that most retrogradely labeled INs are located dorsal to the MNs, in the ventral horn, the intermediate zone and the dorsal horn. IINs predominate in the dorsal horn. CINs are located on average more medially than the IINs in the ventral horn and intermediate zone. Within the IIN and CIN populations, aINs and dINs overlap extensively. The adIINs and adCINs make up only a small fraction of the total number of INs and are scattered throughout much of the respective IIN and CIN domains. The proportions of IINs and CINs are about equal, as are the proportions of aIINs versus dIINs, of aCINs versus dCINs, and of adIINs versus adCINs. The findings are compared to the organization of lumbar spinal INs in other vertebrate species.
Association between Changes in N-Terminal Pro-Brain Natriuretic Peptide Levels and Changes in Left Ventricular Mass Index in Stable Hemodialysis Patients
Authors: Choi So Yeon , Lee Jung Eun , Jang Eun Hee , Kim Min-Ok , Baek Hyunjeong , Ki Chang Seok , Park Seung Woo , Kim Dae Joong , Huh Woo Seong , Oh Ha Young , Kim Yoon-Goo
Published: October 2008

Background/Aims: Left ventricular (LV) hypertrophy is a powerful predictor of mortality in dialysis patients. Serial measurements of LV mass provide prognostic information. We evaluated the association between changes in biomarkers and changes in LV mass index (LVMI) in hemodialysis (HD) patients. Methods: This was a prospective study of 21 stable HD patients with preserved LV ejection fraction (≧50%). Echocardiography and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and cardiac troponin T were performed on the same day and repeated 6 and 12 months later. Results: At baseline, the NT-proBNP and BNP levels correlated with LVMI. Percent changes in LVMI were positively associated with those in log-transformed NT-proBNP levels during both the first (baseline vs. month 6, r = 0.78, p < 0.001) and the second 6 months (months 6 vs. 12, r = 0.73, p < 0.001). Among the 3 biomarkers, NT-proBNP was the only one that was related to changes in LVMI by multivariate correlation analysis, including age, sex, blood pressure, predialysis weight and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Conclusion: Our results show that changes in LVMI are closely correlated with variation in NT-proBNP levels in HD patients. These data have significant implications for the application of NT-proBNP as a biomarker for assessing changes in LVMI in HD patients.
Modifier Effect of the Glu298Asp Polymorphism of Endothelial Nitric Oxide Synthase Gene in Autosomal-Dominant Polycystic Kidney Disease
Authors: Stefanakis N. , Ziroyiannis P. , Trygonis S. , Lamnissou K.
Published: October 2008

Autosomal-dominant polycystic kidney disease (ADPKD) is one of the most common monogenic diseases. It is characterized by a substantial variability in the severity of renal phenotype, primarily assessed by the age at end-stage renal disease (ESRD). The role of modifier genes has been shown in various hereditary diseases, including ADPKD. The gene coding for the endothelial nitric oxide synthase (NOS3) is considered to have a modifier effect on the severity of ADPKD, even if there are studies among different populations that have shown contradictory results. In this study, we investigated the influence of one of the most studied polymorphisms of the NOS3 gene, the Glu298Asp polymorphism, on the age at ESRD in ADPKD. We analyzed a total of 100 ADPKD unrelated patients and 107 healthy cohorts from the Greek population. ADPKD patients were classified into two subgroups: patients with early (rapid progressors) and late (slow progressors) age at ESRD. The results suggested that the Glu298Asp polymorphism of NOS3 gene is associated with the onset age of ESRD. The distribution of C/T alleIes is significantly different between rapid and slow ADPKD progressors leading to the conclusion that the T allele of the Glu298Asp polymorphism of NOS3 gene is associated with earlier progression to ESRD in ADPKD patients.
Evaluation of Genetic Association and Expression Reduction of TRPC1 in the Development of Diabetic Nephropathy
Authors: Zhang Dongying , Freedman Barry I. , Flekac Milan , Santos Elisabete , Hicks Pamela J. , Bowden Donald W. , Efendic Suad , Brismar Kerstin , Gu Harvest F.
Published: October 2008

Background/Aims: The TRPC1 gene on chromosome 3q22–24 resides within the linkage region for diabetic nephropathy (DN) in type 1 (T1D) and type 2 diabetes mellitus (T2D). A recent study has demonstrated that TRPC1 expression is reduced in the kidney of diabetic ZDF- and STZ-treated rats. The present study aimed to evaluate the genetic and functional role of TRPC1 in the development of DN. Methods: Genetic association study was performed with two independent cohorts, including 1,177 T1D European Americans with or without DN from GoKinD population and 850 African-American subjects with T2D-associated end-stage renal disease (ESRD), or with hypertensive (non-diabetic) ESRD, and nondiabetic controls. Seven tag SNP markers derived from HapMap data (phase II) were genotyped. TRPC1 gene expression was examined using real time RT-PCR. Results: No significant association of TRPC1 DNA polymorphisms with DN or ERSD was found in GoKinD and African-American populations. TRPC1 gene mRNA expression in kidney was found to be trendily reduced in 12-week and significantly in 26-week-old db/db mice. Conclusions: TRPC1 genetic polymorphism may not fundamentally contribute to the development of DN, while reduction of the gene expression in kidney may be a late phenomenon of DN as seen in diabetic animal models.
Normalizing NADPH Oxidase Contributes to Attenuating Diabetic Nephropathy by the Dual Endothelin Receptor Antagonist CPU0213 in Rats
Authors: Xu Ming , Dai De-Zai , Dai Yin
Published: October 2008

Background/Aims: NADPH oxidase(NOX) is the main source of reactive oxygen species (ROS) in diabetic nephropathy (DN). Activation of NOX could be mediated via endothelin A (ETAR) and B receptors (ETBR) of the endothelin (ET) system. Thus, CPU0213, a dual ET receptor antagonist, was expected to attenuate DN by suppressing NOX. Methods: Diabetes was produced in male Sprague-Dawley rats 8 weeks after a single injection of streptozotocin (STZ), and treatment with CPU0213 was initiated in the last 4 weeks. Rat mesangial cells (MCs) were incubated with 30 mM glucose for 48 h supplemented with CPU0213 or the NOX inhibitors apocynin and diphenyleneiodonium. Results: After 8 weeks of hyperglycemia, abnormal renal function was associated with oxidative stress and an increased renal weight index in STZ-treated rats. Additionally, upregulation of NOX subunits and the ET system was found in diabetic rats and MCs treated with 30 mM glucose and suppressed by CPU0213 or NOX inhibitors. Except for blood glucose, CPU0213 markedly suppressed these abnormalities in DN. Conclusion: Upregulation of NOX is associated with upregulation of the ET pathway in the pathology of DN. The dual ET receptor antagonist (ETAR and ETBR) CPU0213 effectively normalized renal function in DN by suppressing NOX.
Elevated Osteoprotegerin Levels Predict Cardiovascular Events in New Hemodialysis Patients
Authors: Nishiura Ryosuke , Fujimoto Shouichi , Sato Yuji , Yamada Kazuhiro , Hisanaga Shuichi , Hara Seiichiro , Nakao Hiroyuki , Kitamura Kazuo
Published: October 2008

Background: Patients on hemodialysis (HD) frequently experience cardiovascular events associated with vascular calcification. We investigated the involvement of osteoprotegerin (OPG), an inhibitor of vascular calcification, in the incidence of cardiovascular events and mortality among new HD patients. Methods: We conducted a prospective cohort study of the association of serum OPG levels with morbidity and mortality in subjects who became new HD patients between June 2000 and May 2006. Results: A total of 99 patients (age 58.9 ± 14.6 years, 65 male, 34 female) were prospectively followed up for 41.5 ± 20.2 months. During this period, 27 patients developed cardiovascular events and 12 died of causes related to cardiovascular disease. When divided into 2 groups according to OPG levels, the high OPG group showed a higher prevalence of cardiovascular morbidity and mortality compared with the low OPG group. Cox’s proportional hazards analysis associated the new onset of cardiovascular events with the high OPG group (HR 2.88, 95% CI 1.09–7.62, p = 0.033). Furthermore, the high OPG group at the start of HD was significantly associated with older age, male gender and a high aortic calcification index. Conclusions: Elevated levels of serum OPG in new HD patients may predict subsequent cardiovascular events.
Longitudinal Growth during the First Years of Life: What Is Normal?
Authors: Touwslager R.N.H. , Gerver W.J.M. , Mulder A.L.M. , Gerver Jansen A.J.G.M. , de Bruin R.
Published: October 2008

The anthropometric data of a longitudinal growth study on healthy infants, followed from birth until the age of 4 years and performed during 1995–1999 in The Netherlands, were used to analyze the general growth patterns in terms of height, weight and head circumference, based on z-scores, during the first 4 years of life. The well-known phenomenon where each infant or child tends to decelerate or accelerate its growth velocity depending on its starting position on the reference curve is obvious in this study too. This phenomenon, known as the regression to the mean, is a strong phenomenon especially during the first year. Regression to the mean is calculated for the different age groups as factor. With the given α, it is possible to estimate the individual expectation of growth.
Hashimoto’s Thyroiditis in Down’s Syndrome: Clinical Presentation and Evolution
Authors: Popova Galina , Paterson Wendy F. , Brown Arlene , Donaldson Malcolm D.C.
Published: October 2008

Aim: It was the aim of this study to describe the presentation and clinical course of Hashimoto’s thyroiditis (HT) in children with Down’s syndrome (DS) in 2 Scottish health regions. Patients and Methods: We retrospectively analysed clinical, biochemical and thyroid antibody status in 38 patients with DS with HT diagnosed from 1989 to 2004. Results: The sex distribution was similar (20 males, 18 females), with a median age of 12.3 years (range 2.1–17.7). Of the 38 patients reviewed, 29 were identified by screening. A goitre was present in 6/38 patients. Thyroid antibodies were positive in 36/38 patients, negative in 1/38, and data were unavailable for 1/38. At presentation, 37/38 patients were hypothyroid: 21/37 with compensated hypothyroidism (6 treated initially) and 16/37 with decompensated hypothyroidism (all treated). Of the 15/21 compensated patients who were untreated initially, only 3 remitted while 12 showed disease progression prompting treatment. In the decompensated group, 1/16 patient pursued a fluctuating course between hypo- and hyperthyroidism. The final patient, who was hyperthyroid at presentation, also showed marked fluctuation in thyroid function over a 5-year period. Conclusion: The natural history of HT in DS is unusual, with no female predominance and infrequent goitre in our cohort. While almost all patients required treatment eventually, clinicians should be aware that the disease may pursue a fluctuating course between hypo- and hyperthyroidism.
Hypertriglyceridemia and Ischemic Stroke
Authors: Antonios Nader , Angiolillo Dominick J. , Silliman Scott
Published: October 2008

There are no conclusive data regarding the association between dyslipidemia and the risk of ischemic stroke (IS). Clinical investigations have primarily focused on the association between elevated levels of low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol as stroke risk factors. Much less scientific attention has been aimed at elevated levels of triglycerides. Consequently the potential role of hypertriglyceridemia as an independent risk factor for IS remains controversial. However, accumulating evidence has shown that hypertriglyceridemia is associated with pathophysiological processes such as endothelial dysfunction, atherosclerosis and the production of a prothrombotic state, which could contribute to IS risk. The aim of this review is to critically analyze the contribution of hypertriglyceridemia to the occurrence of IS.
Actigraphy – A Useful Tool for Motor Activity Monitoring in Stroke Patients
Authors: Reiterer Veronika , Sauter Cornelia , Klösch Gerhard , Lalouschek Wolfgang , Zeitlhofer Josef
Published: October 2008

Aim: The aim of the present study was the evaluation of actigraphy as a tool to objectify the recovery process after motor paresis due to stroke. Methods: The motor activity of both arms of patients suffering from stroke was actigraphically recorded at four different time points during the course of rehabilitation: 24–36 h, 5–7 days, 3 months, and 6 months after stroke. Results: Motor activity monitored by wrist-worn actigraphs located at the impaired side revealed an increase in activity between the first two time points and the subsequent ones. Additionally, actigraphic recordings showed lower total motor activity at the impaired side as compared to the nonimpaired side. A significant positive correlation was found between the actigraphically recorded motor activity and the results of the Scandinavian Stroke scale, the Barthel Index, the Rankin Scale Score and with the Motoricity Index during the 1st week, which corresponds to the time when neurological deficits were most pronounced. Conclusion: Our results suggest that actigraphy is a useful tool in the objective evaluation of motor activity after stroke. Moreover, actigraphy covers additional aspects that are not reflected by the usual stroke scales in a clinical situation.