bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Serum Selenium and Total Plasma Homocysteine during the Acute Phase of Ischaemic Stroke
Authors: Angelova Evgeniya A. , Atanassova Penka A. , Chalakova Nedka T. , Dimitrov Borislav D.
Published: October 2008

Background/Aims: Risk of ischaemic stroke (IS) was associated with total homocysteine (tHCY). On the other hand, serum selenium (Se) exhibited anti-aging and cardiopreventive effects. Se and tHCY showed relationships in animals but these were contradictory or inconclusive in humans; therefore, we searched for such associations in acute IS. Methods: Ninety-four participants aged around 47 years were identified and 39 patients versus 46 healthy controls were analysed. Clinical, laboratory (blinded) and risk factor questionnaire methods were used. Comparison, correlation and multifactorial regression analyses were applied. Results: IS patients were similar to controls concerning age and gender. IS was prevalent in the carotid system (76.9%); 82.1% had a subacute onset. IS patients expressed higher tHCY (14.65 ± 9.79 µmol/l) and lower Se levels (1.3 ± 0.5 µmol/l). Twice as many IS patients (23%) had optimal Se levels of <1.01 µmol/l. Subjects with hyperhomocysteinaemia (tHCY ≧15 µmol/l) showed lower Se levels during IS; Se accounted for 15.4% of tHCY variations (R = –0.393; p = 0.015) with unit change increasing tHCY by 8.25 units. Se remained predictive of tHCY levels after adjustments (vitamin B6, fibrinogen, triglycerides). Conclusions: Lower Se was observed during acute IS, being inversely associated with and predicting increased tHCY levels. Of note, there were more IS patients with suboptimal Se than controls.
Evaluation of the Impact of Memantine Treatment Initiation on Psychotropics Use: A Study from the French National Health Care Database
Authors: Vidal Jean-Sébastien , Lacombe Jean-Marc , Dartigues Jean-François , Pasquier Florence , Robert Philippe , Tzourio Christophe , Alpérovitch Annick
Published: October 2008

Background: Clinical studies reported that treatments for Alzheimer’s disease may have an impact on behavioral and psychiatric disorders. We tested the hypothesis that memantine treatment initiation modifies psychotropic medication in real-life practice patients. Methods: A 2-year follow-up cohort study was performed. A sample of patients treated in the general population, extracted from the database of the French national healthcare system (CNAM-TS), was examined. The sample included 4,600 memantine-treated patients (mean age 79.8 years, 69% women) randomly selected from the database of the CNAM-TS covering 69% of the French population aged 65 years and over. The follow-up rate was 95.0%. This database includes exhaustive data on drug consumption. We used interrupted time series analysis of the proportion of psychotropics users (all psychotropic drugs and specific categories) before and after onset of memantine. Results: There was a 39–50% regular increase in patients treated with psychotropic drugs before memantine initiation This increasing trend stopped after memantine initiation, the proportion of psychotropic users remaining stable around 53% up to the end. The trends before and after memantine onset were significantly different (p < 0.001). Conclusions: Our results suggest a temporal relationship between the onset of memantine and the stabilization of psychotropic drugs use in this large sample of elderly patients.
How Imprecise May the Measurement of Fetal Nuchal Translucency Be without Worsening First-Trimester Screening?
Authors: Schmidt P. , Staboulidou I. , Elsässer M. , Vaske B. , Hillemanns P. , Scharf A.
Published: October 2008

Objective: First-trimester screening (FTS) has a trisomy 21 detection rate of about 90%. Despite profound training, the practically reached measurement quality of nuchal translucency (NT) is probably not optimal. This study investigated the impact of measurement errors on FTS. Methods: The data on 10,116 combined FTSs were obtained in a multicenter study. Risk assessment was performed by the JOY software following the Nicolaides risk calculation principles. To investigate the impact of measurement errors, the NT values were artificially altered and the adjusted risks were recalculated. Test performance parameters were obtained and compared with the correct measurements. Results: In this study 85 fetuses were genetically affected. The screening was wrongly inconspicuous in 12 cases and in 479 cases the FTS offered false-positive results. An assumed NT error of ±0.1 mm already causes a highly significant change in the false-positive rate. A difference of –0.2 mm leads to a visible change in false negatives. Discussion: This study demonstrates that even the smallest deviations will significantly affect the false-negative rate. The detection of really diseased fetuses is influenced at a –0.2-mm measurement error. Therefore the NT measurement has to be as precise as possible.
Uterine Prolapse in Pregnancy: A Rare Condition an Obstetrician Should Be Familiar with
Authors: Partsinevelos G.A. , Mesogitis S. , Papantoniou N. , Antsaklis A.
Published: October 2008

Uterine prolapse complicating pregnancy is a rare event. Early recognition is essential in order to avoid possible maternal and fetal risks. We report the case of a 37-year-old pregnant woman who presented to the antenatal outpatient clinic with uterine prolapse at 31+1 weeks of gestation. Sonographic examination revealed an enlarged fibromatous uterus. She was conservatively treated on an inpatient basis. Two weeks later she underwent an emergency cesarean section because of preterm uterine contractions. A live male neonate weighing 1,900 g was delivered. We believe that conservative management with bed rest, followed by an elective cesarean section, may ensure an uncomplicated gestation and an uneventful delivery.
Reversible Conductive Hearing Loss: Restored Activity in the Central Auditory System
Authors: Hutson K.A. , Durham D. , Tucci D.L.
Published: October 2008

The effect of a reversible, unilateral hearing loss on 2-deoxyglucose (2-DG) uptake in the central auditory system was studied using young gerbils. All animals had a unilateral conductive hearing loss (CHL), induced by atresia, on postnatal day 21 (P21). One week later, on P28, animals had their atresia repaired (CHL/R), or not repaired (CHL/NR), and CHL/NR animals entered the 2-DG experiments. CHL/R animals were allowed a 1-week period of restored binaural hearing experience prior to entering 2-DG experiments on P35. Animals in each group were injected with 2-DG and exposed to ambient sounds for 45 min prior to sacrifice. Uptake of 2-DG was measured in the anteroventral cochlear nucleus (AVCN), the medial superior olive (MSO), and the inferior colliculus (IC) on both sides of the brain. In CHL/NR animals, there were significant differences in uptake between the AVCN, MSO, and IC ipsilateral versus contralateral to the manipulated ear, indicating an imbalance in ascending afferent activity. In CHL/R animals, there were no significant differences, suggesting that 1 week after CHL repair, the appearance of balanced afferent activity had been restored.
Effects of Fixative and Embedding Medium on Morphology and Immunostaining of the Cochlea
Authors: O’Malley Jennifer T. , Merchant Saumil N. , Burgess Barbara J. , Jones Diane D. , Adams Joe C.
Published: October 2008

The localization of proteins by immunostaining is a powerful method to investigate otologic disorders. However, the use of fixatives and embedding media (necessary for the preservation of morphology) can obscure antigens, making it difficult to perform immunoassays. We performed a systematic investigation of the effects of fixative and embedding medium on morphology and immunostaining of the mouse cochlea. Three different fixative solutions [4% formaldehyde (F), 4% formaldehyde + 1% acetic acid (FA), and 4% formaldehyde + 1% acetic acid + 0.1% glutaraldehyde (FGA)] and 3 different embedding media (paraffin, polyester wax, and celloidin) were used. Morphology was assessed using light microscopy. Immunostaining was studied using a panel of 6 antibodies (to prostaglandin D synthase, aquaporin 1, connective tissue growth factor, 200-kDa neurofilament, tubulin and Na+,K+-ATPase). Preservation of morphology was suboptimal with paraffin, adequate with polyester wax and superb with celloidin. Immunostaining was successful using all 6 antibodies in all 3 fixatives and all 3 embedding media. While there were differences in strength of signal and localization of antigen between the 3 fixatives, overall, FA and FGA gave the most uniform results. For a given fixative and antibody, there was surprisingly little difference in the quality of immunostaining between celloidin and paraffin, while results in polyester wax were not as good in some cases. These results suggest that celloidin may be the embedding medium of choice for both morphological and pathological studies, including immunostaining when morphology must be optimized.
Expression and Localization of K+ Channels KCNQ2 and KCNQ3 in the Mammalian Cochlea
Authors: Jin Zhe , Liang Gui-Hua , Cooper Edward C. , Järlebark Leif
Published: October 2008

KCNQ1 and KCNQ4 voltage-gated potassium channel subunits play key roles in hearing. Other members of the KCNQ family also encode slow, low voltage-activated K+ M currents. We have previously reported the presence of M-like K+ currents in sensory hair cells, and expression of Kcnq family genes in the cochlea. Here, we describe Kcnq2/3 gene expression and distribution of M channel subunits KCNQ2 and 3 in the cochlea. By using RT-PCR, we found expression of Kcnq2 in the modiolus and organ of Corti, while Kcnq3 expression was also detected in the cochlear lateral wall. Five alternative splice variants of the Kcnq2 gene, one of which has not been reported previously, were identified in the rat cochlea. KCNQ2 and KCNQ3 immunoreactivities were observed in spiral ganglion auditory neurons. In addition, the unmyelinated parts of the nerve fibers innervating hair cells and synaptic regions under hair cells showed KCNQ2 immunoreactivity. KCNQ3 immunoreactivity was also prominent in spiral ganglion satellite cells. These findings suggest that cochlear M channels play important roles in regulation of cellular excitability and maintenance of cochlear K+ homeostasis in the auditory system.
Effects of Sildenafil on Oxidative and Inflammatory Injuries of the Kidney in Streptozotocin-Induced Diabetic Rats
Authors: Jeong Kyung-Hwan , Lee Tae-Won , Ihm Chun-Gyoo , Lee Sang-Ho , Moon Ju-Young , Lim Sung-Jig
Published: October 2008

Background: Oxidative stress and inflammation are implicated in the pathogenesis of diabetic nephropathy. Because sildenafil citrate (Viagra®) has variable cardiovascular benefits, including antioxidative and immunomodulating effects, we investigated its influence on oxidative stress and inflammation in diabetic rat kidney. Methods: Streptozotocin-induced diabetic rats received sildenafil (3 mg/kg/day in drinking water) or not (undosed water) for 8 weeks and were compared to age-matched nondiabetic animals. We evaluated 8-hydroxydeoxyguanosine (8-OHdG; for oxidative DNA damage), inducible nitric oxide synthase (iNOS) and nitrotyrosine (for excessive NO production and peroxynitrite formation), and representative chemoattractants [monocyte chemotactic protein-1, MCP-1; for inflammation and monocyte/macrophage infiltrations (ED-1)] in the kidney. Results: Sildenafil-treated rats had a lower kidney-to-body weight ratio than untreated diabetic rats. Urinary albumin excretion in diabetic rats decreased significantly after sildenafil treatment without changes in systolic blood pressure. Sildenafil-treated rats had significantly lower urinary and renal cortical 8-OHdG levels than the nonsildenafil group. Sildenafil administration significantly attenuated the increased renal nitrotyrosine protein expression, positive iNOS and ED-1 staining in glomeruli and tubulointerstitium, and nitrotyrosine staining in tubulointerstitium. Cortical MCP-1 RNA expression in the sildenafil group was significantly lower than in the nonsildenafil group. Conclusions: Sildenafil treatment may attenuate renal damage by ameliorating oxidative and inflammatory injuries in diabetic rats.
X Pentasomy in an Intracytoplasmic Sperm Injection Pregnancy Detected by Nuchal Translucency Testing
Authors: Cheng Po-Jen , Chueh Ho-Yen , Shaw Sheng-Wen , Hsu Jenn-Jeih , Hsieh T’sang-T’ang , Soong Yung-Kwei
Published: October 2008

Althoughmaternally derived X pentasomy following intracytoplasmic sperm injection (ICSI) is rare, prenatal detection of a case offers insight into etiology and diagnosis. A 29-year-old gravida 1 whose pregnancy resulted from ICSI was referred for ultrasound screening at 11 weeks’ gestation. Nuchal translucency thickness was 3.2 mm, and the fetal nasal bone was absent. Subsequent evaluation revealed karyotype 49,XXXXX. DNA microsatellite analysis showed the extra X chromosomes were maternal in origin. Termination of pregnancy was performed at 15 weeks. Because of the increased risk of sex chromosomal abnormalities in ICSI pregnancies, patients should be counseled prior to fertilization and standard prenatal care should include nuchal translucency measurement and any other elements necessary for indicated pregnancies to obtain a diagnosis.
Promoter Hypermethylation in Tumour Suppressor Genes Shows Association with Stage, Grade and Invasiveness of Bladder Cancer
Authors: Jarmalaite Sonata , Jankevicius Feliksas , Kurgonaite Kristina , Suziedelis Kestutis , Mutanen Pertti , Husgafvel-Pursiainen Kirsti
Published: October 2008

Aims: Superficial bladder cancer is a highly recurrent disease, with progression to muscle invasiveness occurring in 15–30% of cases. Promoter hypermethylation in a panel of tumour suppressor genes involved in cell cycle control, apoptosis and DNA repair was analyzed in superficial bladder tumours in order to evaluate the suitability of epigenetic biomarkers for an earlier prediction of the aggressive course of the disease. Method: Promoter hypermethylation in p16, RARβ, RASSF1A, DAPK, and MGMT genes was analyzed in 58 cases with superficial bladder cancer and 2 cases with benign urological disease using methylation-specific PCR. Results: Promoter hypermethylation was frequently detected in RARβ, RASSF1A and DAPK genes, and 62% of bladder tumours exhibited hypermethylation in at least one gene. The overall frequency of hypermethylation and the number of genes involved increased with tumour stage, grade and muscle invasiveness. Aberrant methylation of RASSF1A and RARβwas predominant (p < 0.05) in muscle-invasive tumours and high-grade tumours, respectively. Cases with concurrent hypermethylation in DAPK, p16 and RARβ genes were moresusceptible to relapse. Conclusion: The results suggest analysis of promoter hypermethylation as a valuable biomarker for prognosis of the aggressive course of disease in bladder cancer.
Decision Making for Relaparotomy in Secondary Peritonitis
Authors: van Ruler O. , Lamme B. , de Vos R. , Obertop H. , Reitsma J.B. , Boermeester M.A.
Published: October 2008

Background/Aims: To provide a qualitative ranking of clinical variables by surgeons that influence their decision for reoperation and to evaluate whether these variables are related to positive findings at relaparotomy. Methods: Importance in decision making for relaparotomy was evaluated for 21 factors using a 10-point visual analogue scale (VAS). Variables with median VAS scores >5.0 were labeled ‘important’. Predictive value for positive findings was evaluated by multivariate analysis. Results: The response rate was 64%. For each variable, a wide range of VAS scores was given. Of variables labeled ‘important’, a diffuse extent of abdominal contamination (odds ratio, OR 1.9; 95% CI 0.99–3.8; p = 0.052), localization of the infectious focus (upper gastrointestinal tract including small bowel: OR 2.6, 95% CI 0.98–7.0, p = 0.055; colon: OR 2.4, 95% CI 0.93–6.0, p = 0.071), and both low (<3 × 109/l: OR 4.6, 95% CI 1.3–17, p = 0.021) and high (>20 × 109/l: OR 2.2, 95% CI 1.0–4.9, p = 0.042) leukocyte counts independently predicted positive relaparotomy. As a set, these variables had only moderate predictive accuracy (c-statistic 0.69). Conclusions: There was no consensus among surgeons which variables were important in decision making for relaparotomy. Only three out of ten variables labeled as ‘important’ were indeed independently predictive, but even as a set had only moderate predictive accuracy.
Speech Performance and Sound Localization in a Complex Noisy Environment in Bilaterally Implanted Adult Patients
Authors: Mosnier Isabelle , Sterkers Olivier , Bebear Jean-Pierre , Godey Benoit , Robier Alain , Deguine Olivier , Fraysse Bernard , Bordure Philippe , Mondain Michel , Bouccara Didier , Bozorg-Grayeli Alexis , Borel Stéphanie , Ambert-Dahan Emmanuèle , Ferrary Evelyne
Published: October 2008

Objective: To evaluate speech performance, in quiet and noise, and localization ability in adult patients who had undergone bilateral and simultaneous implantation. Study Design: Prospective multi-center study. Methods: Twenty-seven adult patients with profound or total hearing loss were bilaterally implanted in a single-stage procedure, and simultaneously activated (Med-El, Combi 40/40+). Subjects were assessed before implantation and at 3, 6 and 12 months after switch-on. Speech perception tests in monaural and binaural conditions were performed in quiet and in noise using disyllabic words, with speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Sound localization measurements were also performed in background noise coming from 5 loudspeakers positioned from –90° to +90° azimuth in the horizontal plane, and using a speech stimulus. Results: There was a bilateral advantage at 12 months in quiet (77 ± 5.0% in bilateral condition, 67 ± 5.3% for the better ear, p < 0.005) and in noise (signal-to-noise ratio +15 dB: 63 ± 5.9% in bilateral condition, 55 ± 6.9% for the better ear, p < 0.05). Considering unilateral speech scores recorded in quiet at 12 months, subjects were categorized as ‘good performers’ (speech comprehension score ≥60% for the better ear, n = 19) and ‘poor performers’ (n = 8). Subjects were also categorized as ‘asymmetrical’ (difference between their 2 unilateral speech scores ≥20%, n = 11) or ‘symmetrical’ (n = 16). The largest advantage (bilateral compared to the better ear) was obtained in poor performers: +19% compared to +7% in good performers (p < 0.05). In the group of good performers, there was a bilateral advantage only in cases of symmetrical results between the 2 ears (n = 10). In the group of poor performers, the bilateral advantage was shown in both patients with symmetrical (n = 6) and asymmetrical results (n = 2). In bilateral conditions, the sound localization ability in noise was improved compared to monaural conditions in patients with symmetrical and asymmetrical performance between the 2 ears. No preoperative factor (age, duration of deafness, use of hearing aids, etiology, etc.) could predict the asymmetrical performance, nor which ear would be the best. Conclusion: This study demonstrates a bilateral advantage (at 12 months after the implantation) in speech intelligibility and sound localization in a complex noisy environment. In quiet, this bilateral advantage is shown in cases of poor performance of both ears, and in cases of good performance with symmetrical results between the 2 ears. No preoperative factor can predict the best candidates for a simultaneous bilateral implantation.
Atenolol Is Inferior to Metoprolol in Improving Left Ventricular Function and Preventing Ventricular Remodeling in Dogs with Heart Failure
Authors: Zacà Valerio , Rastogi Sharad , Mishra Sudhish , Wang Mengjun , Sharov Victor G. , Gupta Ramesh C. , Goldstein Sidney , Sabbah Hani N.
Published: October 2008

Objectives: β-Blockers are standard therapy for patients with heart failure (HF). This study compared the effects of chronic monotherapy with 2 different β1-selective adrenoceptor blockers, namely atenolol and metoprolol succinate, on left ventricular (LV) function and remodeling in dogs with coronary microembolization-induced HF [LV ejection fraction (EF) 30–40%]. Methods: Twenty HF dogs were randomized to 3 months of therapy with atenolol (50 mg once daily, n = 6), metoprolol succinate (100 mg, once daily, n = 7) or to no therapy (control, n = 7). LV EF and volumes were measured before initiating therapy and after 3 months of therapy. The change (Δ) in EF and volumes between measurements before and after therapy was calculated and compared among study groups. Results: In controls, EF decreased and end-systolic volume increased. Atenolol prevented the decrease in EF and the increase in ESV. In contrast, metoprolol succinate significantly increased EF and decreased end-systolic volume. ΔEF was significantly higher and Δend-systolic volume significantly lower in metoprolol succinate-treated dogs compared to atenolol-treated dogs (EF: 6.0 ± 0.86% vs. 0.8 ± 0.85%, p < 0.05; end-systolic volume: –4.3 ± 0.81 ml vs. –1 ± 0.52 ml, p <0.05). Conclusions: In HF dogs, chronic therapy with atenolol does not elicit the same LV function and remodeling benefits as those achieved with metoprolol succinate.
The Renin-Angiotensin-Aldosterone System: Approaches to Guide Angiotensin-Converting Enzyme Inhibition in Patients with Coronary Artery Disease
Authors: Brugts J.J. , den Uil C.A. , Danser A.H.J. , Boersma E.
Published: October 2008

Drugs that modulate the renin-angiotensin-aldosterone system (RAAS) play an important role in modern cardiovascular prevention strategies. Inhibitors of the RAAS, in particular angiotensin-converting enzyme (ACE) inhibitors, have been proven to be beneficial in specific patient groups, including patients with hypertension, heart failure, diabetes mellitus and stable coronary artery disease. Although clinical trials demonstrated a rather consistent beneficial effect of ACE inhibitors across groups of patients based on clinical characteristics, the variability in treatment response on the individual patient level is extensive. Recent publications suggest that genetic polymorphisms in the RAAS are related to cardiovascular risk. Genetic variability also seems associated with the response to ACE inhibitor therapy, and can probably be used to tailor treatment. This review discusses several approaches to guide ACE inhibitor therapy in patients with coronary artery disease. In addition, the potential impact of pharmacogenetics regarding this particular topic is highlighted.
Effect of Penetration Modifiers on the Dermal and Transdermal Delivery of Drugs and Cosmetic Active Ingredients
Authors: Otto A. , Wiechers J.W. , Kelly C.L. , Hadgraft J. , du Plessis J.
Published: October 2008

In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation.
Gender-Specific Weight Estimation of Fetuses between 2,501 and 3,999 g – New Regression Formulae
Authors: Siemer Jörn , Hilbert Antonia , Wolf Tanja , Hart Nicola , Müller Andreas , Schild Ralf L.
Published: October 2008

Objective: To develop new gender-specific regression formulae to estimate fetal weight focusing on a particular weight range from 2,501 to 3,999 g. Methods: 3,254 singleton pregnancies were included to generate new regression formulae for female and male fetuses, and to evaluate their accuracy. Results: In comparison with commonly used formulae, the new gender-specific and weight-range-specific method of fetal weight estimation provided greater accuracy. The mean absolute error was less than 7%. Conclusions: When properly used, the new formulae can improve the accuracy of weight estimations in fetuses between 2,501 and 3,999 g.
Antitumor Activity of a New N-Substituted Thiourea Derivative, an EGFR Signaling-Targeted Inhibitor against a Panel of Human Lung Cancer Cell Lines
Authors: Xiong Xishan , Liu Hong , Fu Lili , Li Lin , Li Jian , Luo Xiaomin , Mei Changlin
Published: October 2008

Epidermal growth factor receptor (EGFR) is one of the important protein tyrosine kinases (PTKs), whose blockade by tyrosine kinase inhibitors (TKIs) has been introduced in the treatment of advanced non-small-cell lung cancers (NSCLCs). However, intrinsic and acquired resistance to the clinically used erlotinib or gefitinib leads to poor overall prognosis. The novel EGFR-TKI will provide alternative choices in NSCLC treatment and might be beneficial. We have previously reported the design and synthesis of a novel class of PTK inhibitors featuring the N-(2-oxo-1,2-dihydro-quinolin-3-ylmethyl)-thiourea framework. In this study, we examined the antitumor effect of compound 5a (DC27) in a panel of human lung carcinoma cell lines. The results of a bromodeoxyurdine (BrdU) incorporation assay revealed that cell proliferation was inhibited in a dose-dependent manner, with an IC50 of 2.5–12.9 µM, similar to gefitinib (1.1–15.6 µM). DC27 induced G₀/G1 arrest of cell cycle and apoptosis as tested by flow cytometry. DC27 markedly reduced tyrosine phosphorylation of EGFR and inhibited activation of Erk1/2 and AKT, two key downstream effectors of proliferation. In conclusion, DC27 has potent in vitro cytotoxicity against human lung carcinoma cells, possibly mediated by induction of apoptosis and cell cycle arrest in G₀/G1 phase.
Correlates of N-Terminal Prohormone Brain Natriuretic Peptides in African Americans with Hypertensive Chronic Kidney Disease: The African American Study of Kidney Disease and Hypertension
Authors: Yi S. , Contreras G. , Miller E.R. , Appel L.J. , Astor B.C.
Published: October 2008

Background/Aims: The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited. Methods: The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20–65 ml/min/1.73 m2) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants. Results: In unadjusted analyses, GFR (r = –0.39; p < 0.001), hematocrit (r = –0.21; p < 0.001) and body mass index (BMI; r = –0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP. Conclusion: Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure.
Diminished Expression of Apical Sodium-Dependent Bile Acid Transporter in Gallstone Disease Is Independent of Ileal Inflammation
Authors: Holzer Arthur , Harsch Simone , Renner Olga , Strohmeyer André , Schimmel Silke , Wehkamp Jan , Fritz Peter , Stange Eduard F.
Published: October 2008

Background: Non-obese gallstone patients exhibit a diminished expression of apical sodium-dependent bile acid transporter (ASBT) in terminal ileum. Crohn’s ileitis demonstrates a significant downregulation of this transporter. Aim: To test whether subclinical ileal inflammation contributes to gallstone disease. Methods: Biopsies from terminal ileum of female subjects with gallstone disease (n = 7), active Crohn’s disease (n = 17) and controls (n = 22) were investigated. mRNA expression of ASBT, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-8, c-jun and c-fos was measured. c-jun and c-fos protein levels were determined and hematoxylin and eosin staining was applied for ileal histology. Results: ASBT expression was comparably low both in gallstone (47% of controls, p = 0.0093) and Crohn’s disease (42% of controls, p = 0.0008). In gallstone disease there was a non-significant trend towards elevated TNF-α and IL-1β, but all cytokines were increased in active Crohn’s disease. c-jun and c-fos were slightly diminished in patients with gallstones. Neither cytokines nor transcription factors correlated significantly with ASBT. The gallstone-associated ileal biopsies exhibited no histological inflammation. Conclusion: Although the expression of ASBT was similarly diminished in both gallstone and Crohn’s disease, subclinical ileal inflammation does not appear to be relevant in gallstone patients. The mechanisms of transcriptional repression of ASBT in both diseases are apparently different.
Fluoride Concentration in Dentin of Exfoliated Primary Teeth as a Biomarker for Cumulative Fluoride Exposure
Authors: dela Cruz G.G. , Rozier R.G. , Bawden J.W.
Published: October 2008

A biomarker for lifetime fluoride exposure would facilitate population-based research and policy making but currently does not exist. This study examined the suitability of primary tooth dentin as a biomarker by comparing dentin fluoride concentration and fluoride exposures. Ninety-nine children’s exfoliated primary teeth were collected from 2 fluoridated and 2 fluoride-deficient communities in North Carolina. Coronal dentin was isolated by microdissection and fluoride concentration assayed using the microdiffusion, ion-specific electrode technique. Information on children’s fluoride exposures since birth from drinking water, toothpaste, supplements, rinses, food and beverages was collected by a self-reported questionnaire administered to caregivers. Only a small portion of the variance (10%) in incisor dentin fluoride (mean 792, SD 402 mg/kg) was accounted for by the best linear regression model as evaluated by the adjusted R2. A moderate portion of the variance (60%) of molar dentin fluoride (mean 768, SD 489 mg/kg) was predicted by dietary fluoride supplement exposures, community of residence, and frequent tea consumption. Results for molars suggest that primary tooth dentin concentration may prove to be a satisfactory biomarker for fluoride exposure.
Effects of Different Kinds of Fluorides on Enolase and ATPase Activity of a Fluoride-Sensitive and Fluoride-Resistant Streptococcus mutans Strain
Authors: van Loveren C. , Hoogenkamp M.A. , Deng D.M. , ten Cate J.M.
Published: October 2008

Enolase and ATPase are sensitive to fluoride. It is unclear whether this sensitivity differs for F-sensitive and F-resistant cells or for different types of fluoride. Permeabilized cells of the fluoride-sensitive strain Streptococcus mutans C180-2 and its fluoride-resistant mutant strain C180-2 FR were preincubated at pH 7 or 4 with NaF, the amine fluorides Olaflur and Dectaflur and amine chloride controls. After preincubations, enolase and ATPase activities of the cells were assessed. Enolase activity was more inhibited after preincubation at pH 7 with NaF than with Olaflur. Amine chloride stimulated, although not with statistical significance, the enolase activity of both strains. After preincubation at pH 4 the enolases were strongly inactivated, but the fluoride-resistant strain’s enolase to a lesser extent. The results suggested that amine acts to protect enolase activity against the detrimental low pH effect. Gene sequencing showed that the enolase genes of the fluoride-resistant and fluoride-sensitive strain were identical. ATPase activity was not reduced after NaF preincubation at either pH 7 or pH 4. The amine fluorides and their chloride controls in the preincubation mixture reduced the ATPase activity significantly at both pH values. In conclusion, our results showed that preincubation with amine fluoride did not inhibit enolase activity more effectively than NaF. The amine part of the molecule may protect enolase activity against preincubations at low pH. ATPase activity was not inhibited by NaF preincubation but was significantly inhibited after preincubation with amine fluorides and amine chlorides.
Local versus General Anaesthesia with Prolene Hernia System Mesh for Inguinal Hernia Repair: Early and Long-Term Outcomes
Authors: Sanjay P. , Woodward A.
Published: October 2008

Background: There are minimal data regarding the feasibility of Prolene Hernia System repair under local anaesthesia and patient acceptability. This study analyses the outcomes of Prolene Hernia System repair under different anaesthetic techniques. Methods: A retrospective review of all Prolene Hernia System repairs over a 5-year period was performed. The outcome measures were type of anaesthesia used, early and late complications, recurrence and patient satisfaction. Results: 100 repairs were analysed. Seventy repairs were performed under local anaesthesia and 30 under general anaesthesia. The number of patients with a body mass index >30 were 17 (24%) and 8 (27%), respectively, in the local- and general-anaesthesia groups (p = 0.7). Day cases were higher in the local-anaesthesia group (69 days vs. 16 days, p = 0.001). Early complications were similar in the two groups. 18 (26%) patients in the local-anaesthesia group and 6 (19%) in the general-anaesthesia group developed chronic groin pain (p = 0.6). One recurrence was noted in the local-anaesthesia group. Patient satisfaction was high with both anaesthetic techniques. Conclusions: Prolene Hernia System repair under local anaesthesia results in increased day cases with similar complication rates compared to general anaesthesia. Both anaesthetic techniques are associated with good outcomes and excellent patient satisfaction.
Phase II Trial of S-1 in Combination with Oxaliplatin in Previously Untreated Patients with Recurrent or Inoperable Biliary Tract Cancer
Authors: Oh Sung Yong , Lee Gyeong-Won , Kim Hoon Gu , Kim Tae Hyo , Kim Hyun Jin , Kang Jung Hun
Published: October 2008

Background: Biliary tract cancers are among the most aggressive tumors with a poor prognosis. We conducted a phase II study on combination chemotherapy consisting of S-1 and oxaliplatin in previously untreated patients . Methods: Patients were treated with S-1 40 mg/m2 twice daily, administered orally on days 1–28, and 85 mg/m2 of oxaliplatin, administered via an intravenous 90-min infusion on days 1, 15 and 29. Treatments were repeated every 6 weeks. Results: 15 patients were enrolled: 9 patients (60%) had intrahepatic and 3 (20%) had extrahepatic cholangiocarcinoma, 2 (13.3%) had cancer of the ampulla of Vater and 1 patient had gall bladder cancer. Partial response was observed in 1 of the 15 (6.7%) patients. Stable disease was observed in 4 patients (26.7%). The median time to progression was 1.4 months (95% confidence interval, CI, 0.9–1.9), and the median overall survival was 3.1 months (95% CI, 0.0–7.0). Grade 3 hematologic toxicities included neutropenia (1, 6.7%) and thrombocytopenia (1, 6.7%). As the response rate in stage I did not justify progression to stage II (≧2/15), this study had to be discontinued in accordance with the established protocols. Conclusion: The combination chemotherapy with S-1 and oxaliplatin utilized in this study resulted in no promising antitumor activity.
Gefitinib Increases Serum Concentrations of Oral Irinotecan and SN-38 without Increasing the Biliary Concentration of SN-38 in Rats
Authors: Nakamura Yoichi , Satake Kurika , Sano Kazumi , Ito Akiko , Yoshikawa Megumi , Ikegami Yoji , Yoshida Hisahiro , Nakano Hirofumi , Oka Mikio , Sawada Seigo , Soda Hiroshi , Kohno Shigeru
Published: October 2008

Background: Gefitinib competes with topoisomerase I inhibitors at drug efflux pumps in vitro. We evaluated the effects of oral gefitinib on pharmacokinetic parameters of orally coadministered irinotecan. Methods: We measured the serum pharmacokinetic parameters and biliary excretion of irinotecan, SN-38 and its glucuronide after irinotecan (50 or 100 mg/kg) was orally administered with or without gefitinib 100 mg/kg to rats. We measured the concentrations of irinotecan and SN-38 in the small intestine, liver, lungs and kidneys in each rat. Results: The plasma area under the curve (0–24 h) of irinotecan and SN-38 was increased significantly, while the apparent elimination constant of irinotecan was decreased significantly. Gefitinib significantly increased the biliary cumulative amounts of irinotecan, but not of SN-38, and also influenced the enterohepatic circulation of irinotecan, but not of SN-38. Conclusions: Gefitinib increased the serum concentrations of irinotecan and SN-38 following oral administration of irinotecan without increasing the biliary excretion of SN-38 in vivo.
Association of A/G Polymorphism in Intron 13 of the Monoamine Oxidase B Gene with Schizophrenia in a Spanish Population
Authors: Gassó Patricia , Bernardo Miquel , Mas Sergi , Crescenti Anna , Garcia Clemente , Parellada Eduard , Lafuente Amalia
Published: October 2008

Background: Monoamine oxidase B (MAO-B) enzyme is involved in the oxidative metabolism of dopamine. We studied whether the A644G polymorphism in intron 13 of the MAO-B gene is a risk factor for schizophrenia. Methods: 242 subjects diagnosed with schizophrenia and related disorders and 290 hospital-based controls participated in the study. Genomic DNA was isolated from whole blood and genotyped with the allele-specific oligonucleotide polymerase chain reaction method. Results: This polymorphism was studied by diagnosis subgroups and the G allele was identified as a risk factor for developing schizophrenia (p = 0.006). When we performed a sex-specific analysis, the G allele was only a risk factor for developing schizophrenia in women (p = 0.01). Although the frequency of the G allele is higher in male patients than in male controls, no statistically significant association with schizophrenia was found. Conclusion: Our results support the involvement of the MAO-B gene in schizophrenia, particularly in women.
Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and Childhood-Onset Mood Disorders
Authors: Misener V.L. , Gomez L. , Wigg K.G. , Luca P. , King N. , Kiss E. , Daróczi G. , Kapornai K. , Tamas Z. , Mayer L. , Gádoros J. , Baji I. , Kennedy J.L. , Kovacs M. , Vetró Á. , Barr C.L.
Published: October 2008

Background/Aims: Inflammatory cytokines induce a behavioral syndrome, known as sickness behavior, that strongly resembles symptoms typically seen in depression. This resemblance has led to the theory that an imbalance of inflammatory cytokine activity may be a contributing factor in depressive disorders. Support for this is found in multiple lines of evidence, such as the effects of cytokines on the activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain-derived neurotrophic factor, and hippocampal function, all of which are implicated in the etiology of depression. In addition, associations between inflammatory activity and depressive symptomology have been documented in a number of studies, and the depressogenic effects of cytokine therapy are well known. Accordingly, given that depression has a substantial genetic basis, genes involved in the regulation of inflammatory cytokine activity are strong candidates for involvement in genetic susceptibility to depressive disorders. Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and IL10, as candidates for involvement in childhood-onset mood disorders. Methods: In this study of 384 families, each ascertained through a child with depression diagnosed before the age of 15 years, 11 polymorphisms of known or likely functional significance (coding and regulatory variants) were analyzed. Results: Testing for biased transmission of alleles from parents to their affected offspring, we found no evidence for an association between childhood-onset mood disorders and any of the polymorphisms, either individually or as haplotypes. Conclusion: The present study does not support the involvement of the TNF, IL1A, IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to early-onset mood disorders.
Disposition of Naltrexone after Intravenous Bolus Administration in Wistar Rats, Low-Alcohol-Drinking Rats and High-Alcohol-Drinking Rats
Authors: Akala Emmanuel O. , Wang Hu , Adedoyin Adedayo
Published: October 2008

Reports have shown that interspecies differences in the metabolism and pharmacokinetics of naltrexone are a rule rather than exception. However, there is paucity of information on the disposition of naltrexone in selectively bred rat lines that reliably exhibit high and low voluntary alcohol consumption, and are often used to study alcohol-drinking behavior. We have characterized the pharmacokinetic profiles of naltrexone in selectively bred rat lines: high-alcohol-drinking (HAD-1) and low-alcohol-drinking (LAD-1) rats as well as the native Wistar strain. This study was carried out to establish a baseline pharmacokinetic profile of naltrexone in these rats prior to evaluating its pharmacokinetic profile in polymeric controlled-release formulations in our laboratory. The hypothesis is that alcohol-preferring and non-alcohol-preferring lines of rats should differ in the disposition of intravenously administered naltrexone. Naltrexone administration and blood collection were via the jugular vein. In a parallel experiment, naltrexone was administered via the jugular vein, but urine was collected using the Nalgene metabolic cage system. Data were analyzed by a noncompartmental approach. Results show a high clearance that is close to or higher than hepatic blood flow in all groups (Wistar > LAD-1 > HAD-1, but with a statistically significant difference only between Wistar and HAD-1). Volume of distribution (∼2.5–3 l/kg) and the half-life (∼1 h) were similar. Urinary elimination of naltrexone was small, but also showed differences between the rats: HAD-1 > LAD-1 > Wistar, but with a statistically significant difference only between HAD-1 and Wistar rats. This study has therefore established the baseline disposition characteristics of naltrexone in these strains of rats.
Increased Accuracy of Fetal Weight Estimation with a Gender-Specific Weight Formula
Authors: Siemer Jörn , Wolf Tanja , Hart Nicola , Schrauder Michael , Meurer Britta , Goecker Tamme , Beckmann Matthias W. , Schild Ralf L.
Published: October 2008

Objective: To test whether Schild’s sex-specific formula for estimating fetal weight is more accurate than commonly used regression formulae. Methods: The gender-specific formula and 10 widely used equations were evaluated in a group of 989 pregnancies. Each fetus underwent ultrasound examination with complete biometric parameters within 7 days before delivery. Results: Over the whole weight range and in the subgroup of newborns with a birth weight between 2,500 and 3,999 g, the sex-specific weight formula from Schild demonstrated the best level of accuracy. For infants with a birth weight of less than 2,500 g as well as for macrosomic newborns, the gender-specific formula did not improve fetal weight estimation. Conclusion: In pregnancies where fetal gender is known, Schild’s regression formula should be used when fetal weight lies within the range of 2,500–3,999 g.
Statistical Parametric Analysis of Cerebral Blood Flow in Vascular Dementia with Small-Vessel Disease Using 99mTc-HMPAO SPECT
Authors: Kato Hiroki , Yoshikawa Takuya , Oku Naohiko , Imaizumi Masao , Takasawa Masashi , Kimura Yasuyuki , Kajimoto Katsufumi , Tanaka Makiko , Kitagawa Kazuo , Hori Masatsugu , Hatazawa Jun
Published: October 2008

Background: Subcortical ischemic vascular dementia (SVD) caused by small-artery disease is a major cause of dementia. It still remains unclear, however, whether SVD may present with localized regional cerebral blood flow (rCBF) changes. We aimed to clarify the local rCBF changes associated with dementia in patients with early-stage SVD. Methods: The subjects consisted of 15 patients with early-stage SVD [Mini Mental State Examination (MMSE) score: 20 ± 3.5] without apparent brain atrophy (SVD group), 11 patients without dementia with white matter lesions (non-dementia-WML group) and 16 age-matched controls. All the subjects were right-handed and underwent brain perfusion single photon emission computed tomography (SPECT), magnetic resonance imaging and cognitive function testing. Statistical analysis of the differences in the SPECT rCBF was performed by SPM2. The degree of severity of the WMLs was evaluated based on the Scheltens rating scale. Results: The results of SPM analysis revealed that the rCBF in the SVD group was significantly decreased in the pulvinar nuclei of the thalamus of both sides as compared with that in the controls, and in the left pulvinar nucleus as compared with that in the non-dementia-WML group. On the other hand, SPM analysis revealed no significant reduction in rCBF in the non-dementia-WML group as compared with that in the controls. The WMLs in the left parietal region were severer in the SVD group than in the non-dementia-WML group. Conclusions: In patients with early-stage SVD without apparent brain atrophy, significant rCBF reduction in the bilateral pulvinar nuclei as compared with that in normal controls, and in the left pulvinar nucleus as compared with that in patients without dementia with WMLs was found.
Prenatal Diagnosis of an Epignathus Associated with a 49,XXXXY Karyotype – A Case Report
Authors: Staboulidou Ismini , Miller Konstantin , Göhring Gudrun , Hillemanns Peter , Wüstemann Max
Published: October 2008

Background: Epignathus is a rare form of congenital teratoma, originating from the base of the skull, most commonly the hard palate, or mandible. It has been associated with a poor prognosis due to complications including polyhydramnios and respiratory compromise at birth as a consequence of upper airway obstructions. It is usually not associated with chromosomal aberrations. We present a case of prenatally diagnosed epignathus associated with a gonosomal pentasomy 49,XXXXY. Case: A 34-year-old gravida 1, para 0 was referred to our unit with a sonographically suspected gastroschisis at 26+6 weeks’ gestation. A detailed ultrasound scan revealed a large mixed echogenic mass seen in continuation with the mouth in the midline. Based on the appearance, an epignathus was suspected. No other fetal anomalies were detected. Karyotyping showed a 49,XXXXY karyotype of the fetus. The couple decided to continue the pregnancy after detailed counseling about results and prognosis. A cesarean section was necessary and performed at 29+0 weeks’ gestation due to a pathological Doppler and cardiotocogram. Because of the enormous epignathus intubation of the newborn was not possible. A tracheostomy was performed for ventilation and oxygenation, which failed and the newborn died 30 min after birth. Conclusion: Prenatal diagnosis by ultrasound has improved perinatal management. This should include assessment of the tumor size and spread in order to establish an accurate prognosis and to anticipate likely problems which are to be encountered during pregnancy or at the time of delivery. To our knowledge, this is the first reported case of a prenatally diagnosed epignathus with a gonosomal pentasomy 49,XXXXY.