bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Detecting Extrahepatic Metastasis in Pretreatment Staging of Hepatocellular Carcinoma
Authors: Yoon Ki Tae , Kim Ja Kyung , Kim Do Young , Ahn Sang Hoon , Lee Jong Doo , Yun Mijin , Rha Sun Young , Chon Chae Yoon , Han Kwang-Hyub
Published: December 2007

Objectives:18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for differentiating benign from malignant lesions, evaluating tumor stage, monitoring the response to therapy and detecting tumor recurrence in a variety of malignancies. Nevertheless, its use in patients with hepatocellular carcinoma (HCC) is still uncertain. We evaluated whether FDG-PET has a role in detecting extrahepatic metastasis in pretreatment tumor staging of HCC and the characteristics of patients with extrahepatic metastasis that benefit from FDG-PET. Methods: Eighty-seven patients with HCC underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and chest X-ray to evaluate pretreatment tumor staging. FDG-PET was then performed to detect extrahepatic metastasis. The power of FDG-PET to detect extrahepatic metastasis was compared with that of conventional images. In addition, we evaluated whether the detection of extrahepatic metastasis using FDG-PET changed the TNM stage. Moreover, we investigated the clinical and tumor characteristics of patients with extrahepatic HCC metastasis. Results: Extrahepatic metastases were identified in 24 of 87 patients. The location and frequency of metastases were lung 12, lymph nodes 19 and bone 11. All of the extrahepatic metastases were detected by FDG-PET. In addition, FDG-PET identified 4 lymph node metastases and 6 bone metastases that were not found using conventional methods. The initial TNM stage based on the conventional staging workup was changed in 4 cases after FDG-PET. Extrahepatic metastasis was significantly more frequent in patients with intrahepatic tumor >5 cm in size (p = 0.045). Conclusions: FDG-PET is a useful imaging modality for identifying extrahepatic metastases which may lead to accurate staging and proper management of patients with possible extrahepatic metastases.
Percutaneous Radiofrequency Ablation of Sonographically Unidentifiable Liver Tumors
Authors: Minami Yasunori , Kudo Masatoshi , Chung Hobyung , Inoue Tatsuo , Takahashi Shunsuke , Hatanaka Kinuyo , Ueda Taisuke , Hagiwara Hitoshi , Kitai Satoshi , Ueshima Kuzuomi , Fukunaga Toyokazu , Shiozaki Hitoshi
Published: December 2007

Objective: The purpose of this study was to evaluate the safety and feasibility of a real-time integrated system with computed tomography (CT) and sonographic images for radiofrequency (RF) ablation of hepatic malignancies poorly defined on B-mode sonography, and to clarify the suitable phase of CT images for using this virtual sonography. Methods: Between September 2004 and December 2004, 12 patients with 16 hepatocellular carcinomas and two metastatic lesions arising from colorectal adenocarcinoma (n = 1) and rectal carcinoid (n = 1) were treated. The maximum diameter of nodules ranged from 1.0 to 2.5 cm (mean ± SD; 1.5 ± 0.6 cm) on CT images. Results: Complete tumor necrosis was achieved in a single session in 19 lesions (90%), while a second session was required for the remaining two lesions (10%). Portal phase multi-planar reconstruction images were displayed under a suitable position corresponding to the ultrasound images in 9 patients (HCC = 7, metastasis = 2), and arterial phase multi-planar reconstruction images were displayed in the 3 remaining patients with hepatocellular carcinoma. Conclusion: Percutaneous RF ablation guidance using virtual sonography is an effective treatment for patients with hepatic malignancies. The portal phase of CT images may be the most suitable to indicate the 3-dimensional relationship between the liver vasculature and tumors on virtual sonography.
Pain-Related Activation of Leukocyte Cellular Adhesion Molecules: Preliminary Findings
Authors: Griffis Charles A. , Irwin Michael R. , Martinez-Maza Otoniel , Doering Lynn , Nyamathi Adeline , Kaufman Robert , Elashoff David , Aziz Najib , Compton Peggy
Published: December 2007

Background/Aims: Acute adrenergic stressors have been found to activate neuroendocrine pathways that can alter leukocyte migration and activity. Leukocyte migration is known to affect the pathophysiology of inflammatory disease processes. This study examined the effects of acute experimental pain on catecholamine and cortisol levels and leukocyte expression of cellular adhesion molecules. Methods: Healthy subjects (n = 10) underwent 45 min of acute experimental pain using earlobe electrical stimulation. Measures included sensory and affective pain responses, perceived stress, circulating levels of catecholamines, cortisol, and expression of integrin (CD11a+) cellular adhesion molecules on leukocyte subsets. Data were collected at baseline, after 22.5 and 45 min of pain, and 180 min after pain cessation. Results: Experimental pain acutely increased circulating levels of epinephrine, along with increases in the number of CD8+CD11a+ leukocytes and the density of CD11a molecules on CD8+ cells. Positive correlations were found between pain and stress scores, and the number of CD8+CD11a+ leukocytes. Conclusion: Acute pain induces elevated cellular adhesion molecule expression on leukocytes, which has possible implications for increasing leukocyte infiltration and disease exacerbation in patient populations with inflammatory syndromes.
Disturbance of Serum Interleukin-2 and Interleukin-8 Levels in Posttraumatic and Non-Posttraumatic Stress Disorder Earthquake Survivors in Northern China
Authors: Song Yuqing , Zhou Dongfeng , Guan Zhenquan , Wang Xiangdong
Published: December 2007

Objective: It is evident that immune cytokines are involved in the pathophysiology of posttraumatic stress disorder (PTSD), but results of different studies are still inconsistent. Here, serum interleukin (IL)-2, IL-6 and IL-8 levels were compared between earthquake survivors with PTSD, those with non-PTSD and normal controls to investigate whether there is any relationship between cytokine levels and PTSD. In addition, the relationship of these cytokines with psychological parameters of the disorder was examined as well. Methods: Thirty-four earthquake survivors with PTSD (according to DSM-IV criteria), 30 earthquake survivors with non-PTSD and 34 controls were recruited in northern China using the Composite International Diagnostic Interview instrument. Serum IL-2, IL-6 and IL-8 levels were compared. IL-2 levels were measured by radioimmunometric assay, while serum IL-6 and IL-8 levels were measured using sandwich enzyme-linked immunosorbent assay. Psychological symptoms were assessed using 3 subscales of the Symptoms Checklist (SCL-90-R), including depression, anxiety and somatization. Results: Only earthquake survivors diagnosed with PTSD had significantly lower serum IL-8 levels. Also, we found that earthquake survivors (either with PTSD or non-PTSD) had significantly lower serum IL-2 levels and more severe psychological symptoms. The severity of depressive and anxiety symptoms in earthquake survivors was positively related to serum IL-6 levels. Conclusions: PTSD may be associated with a reduced level of serum IL-8, and traumatic survivors may be associated with a lower level of serum IL-2.
Acquired Heart Block: A Possible Complication of Patent Ductus Arteriosus in a Preterm Infant
Authors: Grasser Monika , Döhlemann Christoph , Mittal Rashmi , Till Holger , Dietz Hans-Georg , Münch Georg , Holzinger Andreas
Published: December 2007

A large patent ductus arteriosus (PDA) is a frequently encountered clinical problem in extremely low birth weight (ELBW) infants. It leads to an increased pulmonary blood flow and in a decreased or reversed diastolic flow in the systemic circulation, resulting in complications. Here we report a possible complication of PDA not previously published. On day 8 of life, a male ELBW infant (birth weight 650 g) born at a gestational age of 23 weeks and 3 days developed an atrioventricular block (AV block). The heart rate dropped from 168/min to 90/min, and the ECG showed a Wenckebach second-degree AV block and intraventricular conduction disturbances. Echocardiography demonstrated a PDA with a large left-to-right shunt and large left atrium and left ventricle with high contractility. Within several minutes after surgical closure of the PDA, the heart rate increased, and after 30 min the AV block had improved to a 1:1 conduction ratio. Echocardiography after 2 h revealed a significant decrease of the left ventricular and atrial dimensions. Within 12 h, the AV block completely reversed together with the intraventricular conduction disturbances. We suggest that PDA with a large left-to-right shunt and left ventricular volume overload may lead to an AV block in an ELBW infant. Surgical closure of the PDA may be indicated.
In vitro Fertilization in Normoresponder Patients with Endometriomas: Comparison with Basal Simple Ovarian Cysts
Authors: Kumbak Banu , Kahraman Semra , Karlikaya Guvenc , Lacin Selman , Guney Aysun
Published: December 2007

Objective: To investigate whether the space-occupying effect of an endometrioma, rather than endometriosis itself, affects results in in vitro fertilization (IVF) using women with simple ovarian cysts as the control group. Methods: 85 normoresponder patients with endometriomas of 10–50 mm who underwent IVF treatment directly without initial removal were compared with 83 normoresponder patients with simple ovarian cysts of 10–35 mm detected at the beginning of stimulation and initiated treatment without aspiration. Results: Gonadotropin consumption was higher in the endometrioma group (3,013 vs. 2,451 IU; p = 0.001), although significantly fewer numbers of oocytes were retrieved (13.9 vs. 16.4; p = 0.03). However, oocyte maturation rates were similar. The transferred grade I embryos ratio was evaluated and found to be better in the cyst group (79.7 vs. 70.7%; p = 0.03). Consequently, the implantation rate was found to be significantly higher in the cyst group (28 vs. 19%; p = 0.02), although pregnancy and ongoing pregnancy rates were similar. Conclusion: The presence of an endometriotic cyst during the IVF cycle was demonstrated to be associated with a lower embryo quality and implantation rate, although pregnancy success was unaffected. This adverse effect is suggested to be the result of the disease itself, not the presence of a cystic mass.
Hyperproduction of Inhibitor-Susceptible TEM β-Lactamase Is Responsible for Resistance of Serratia marcescens to β-Lactam-β-Lactamase Inhibitor Combinations
Authors: Zhao Wei-Hua , Hu Zhi-Qing , Chen Gelin , Ito Ribu , Shimamura Tadakatsu
Published: December 2007

Background: Some clinical isolates of Serratia marcescens showed high-level resistance to expanded-spectrum cephalosporins alone and in combination with β-lactamase inhibitor, but the β-lactamase extracted from these strains was sensitive to the inhibitors. This study examines the possible mechanisms responsible for the discrepancy. Methods and Results: Three clinical isolates of S. marcescens bore the blaTEM gene coded on a plasmid. This was confirmed by detection of the bla gene using PCR analysis and by transferring resistance determinants to Escherichia coli via conjugation and transformation. All of the E. coli transconjugants and transformants acquired a similar level of resistance to penicillins and narrow-spectrum cephalosporins, and showed the reduced susceptibility to expanded-spectrum cephalosporins alone and in combination with clavulanate. As a result of the highly constitutive expression of the TEM gene, up to 247–690 U of β-lactamase were produced by 1010 cells of wild-type S. marcescens and the transconjugants and transformants. In the presence of 0.24 U/ml of TEM enzyme, the minimum inhibition concentrations of cefotaxime against E. coli ATCC 25922 increased from 0.125 to 512 µg/ml. The TEM-type β-lactamase extracted from these strains was sensitive to clavulanate, and 62.2–92.1% of its activity was inhibited after preincubation with 0.1 mM clavulanate. Conclusion:The TEM-type β-lactamase plays a critical role in the resistance of S. marcescens to β-lactams, and the hyperproduction of inhibitor-susceptible TEM β-lactamase is responsible for the resistance to β-lactam-β-lactamase inhibitor combinations.
Can a Peripheral Artery Be Used to Detect Venous to Arterial Circulation Shunts?
Authors: Daly Kevin J. , Hutchinson Suzanne , McCollum Charles N.
Published: December 2007

Background: Transcranial Doppler is a sensitive test for patent foramen ovale (PFO), but an absent temporal window precludes this in 12–15% of patients. We investigated whether the brachial (BrA), common carotid (CCA) or common femoral (CFA) artery provided reliable alternatives. Methods: Patients underwent simultaneous insonation of a middle cerebral artery (MCA, n = 66) and either (a) the BrA (n = 22), (b) CCA (n = 20) or (c) CFA (n = 24) with a 2-MHz transcranial Doppler probe. Results: The correlation between microbubble emboli counts in the MCA and the peripheral arteries was (a) r = 0.67 (95% CI 0.53–0.77) for the BrA, (b) r = 0.80 (95% CI 0.71–0.87) for the CCA and (c) r = 0.92 (95% CI 0.89–0.95) for the CFA. The agreement for detection of PFO was best using the CFA with a kappa of 0.95 (95% CI 0.66–1.0). Conclusion: The CFA is a simple and reliable alternative to the MCA, but the criteria for diagnosis of a PFO are different.
Intravenous Thrombolysis with rt-PA in Acute Ischemic Stroke Patients Aged Older than 80 Years in Italy
Authors: Toni Danilo , Lorenzano Svetlana , Agnelli Giancarlo , Guidetti Donata , Orlandi Giovanni , Semplicini Andrea , Toso Vito , Caso Valeria , Malferrari Giovanni , Fanucchi Simona , Bartolomei Luigi , Prencipe Massimiliano
Published: December 2007

Background: Intravenous (i.v.) thrombolysis with rt-PA within 3 h from symptom onset is the only approved treatment of pharmacological revascularization in acute ischemic stroke. However, little information exists on its use in elderly patients, in particular those aged >80 years, who at present are excluded from treatment. Methods: In a multicenter Italian study on i.v. thrombolysis, patients aged >80 years (n = 41) were compared with those aged ≤80 years (n = 207) regarding the percentage of symptomatic (nonfatal and fatal) intracerebral hemorrhage (SICH), favorable 3-month functional outcome (modified Rankin Scale score 0–2) and poor outcome (death or dependence, i.e. modified Rankin Scale score 3–5). Results: The percentage of SICH (nonfatal and fatal) was comparable between older (2.4%, 2.4%) and younger (2.4%, 2.4%) patient groups (p = 1.0). At 3 months, favorable outcome occurred in 44% and dependence in 22% of the older, and respectively in 58.5 and in 30.9% of the younger patients (p = 0.897). Patients aged >80 years had a higher mortality (34.1%) as compared to those aged ≤80 years (10.6%) (p < 0.001). Baseline National Institute of Health Stroke Scale score was the only statistically significant predictor of both mortality (OR = 1.26; 95% CI = 1.07–1.50) and poor outcome (OR = 1.39; 95% CI = 1.14–1.68) in the >80-year-old group. Conclusions: Acute ischemic stroke patients aged >80 years treated with i.v. rt-PA have a higher mortality than younger patients, but there are no differences for SICH nor for favorable outcome. Our data suggest that thrombolytic therapy should not be a priori denied for appropriately selected >80-year-old patients but randomized controlled clinical trials are necessary before definite recommendations can be given.
Genetics and Gene-Environment Interactions in Atopic Diseases
Authors: Håberg Siri E. , Nafstad Per , Nystad Wenche , Magnus Per
Published: December 2007

Objectives: The Norwegian Mother and Child Cohort Study (MoBa) aims to provide new insights in a broad variety of diseases. The goal of the study is to understand pathways in disease development, and identify preventive measures. Several designs are suitable for studying genetics in complex diseases like asthma and allergy, in MoBa. Methods: MoBa is a prospective population based cohort of 100 000 pregnancies, following offspring into adulthood. Enrollment started in 1999, and will be completed in 2008. A biobank with samples from the mother, father and child, together with detailed questionnaires from early pregnancy and childhood constitute the basis of the study. When studying complex diseases like asthma, a design with case-parent triads is useful. Parental effects and interactions between maternal and fetal genes can be detected. Stratifying triads by environmental exposure enables assessment of gene-environment interactions. Results: By July 2006, more than 73,000 pregnancies have been included, with nearly 7,000 siblings and 1,300 pairs of twins enrolled. Biological samples are processed and stored at the biobank. The first children are reaching age seven in 2006. Conclusion: The MoBa cohort provides an excellent basis for studying genetic, epigenetic and environmental influences on complex diseases.
Oxidized Low-Density Lipoproteins, Autoantibodies against Oxidized Low-Density Lipoproteins and Carotid Intima Media Thickness in a Clinically Healthy Population
Authors: Chen Haw-Wen , Kuo Ching-Ling , Huang Ching-Shan , Kuo Shou-Jen , Liu Chin-San
Published: December 2007

Background: Oxidized low-density lipoproteins (oxLDLs) play an important role in the progress of atherosclerosis. Autoantibodies (oxLDL Ab) against oxLDLs may reflect the extent of LDL oxidation in vivo. Our aim was to investigate the correlation between oxLDLs, oxLDL Ab and intima media thickness of the common carotid arteries (CCA-IMT) in a clinically healthy population. Methods: Two hundred subjects were recruited, and demographic and clinical characteristics of the subjects were recorded. By use of tertile classification of plasma oxLDLs and oxLDL Ab, 9 groups including 4 extreme subject groups were generated. CCA-IMT was measured as an indicator of carotid atherosclerosis. Results: Age and plasma LDL concentration contributed significantly to CCA-IMT (p < 0.05). Body mass index, smoking index and plasma LDL concentration were significantly positively related to the plasma oxLDLs concentration; by contrast, plasma oxLDL Ab were significantly negatively related to the plasma oxLDL concentration (p < 0.05). Subjects in the group with low oxLDL Ab/high oxLDLs had the greatest CCA-IMT and the highest level of LDL; by contrast, subjects in the group with high oxLDL Ab/low oxLDLs had the least CCA-IMT and the lowest level of LDL. Conclusions: Both plasma oxLDLs and oxLDL Ab contribute, although in opposite ways, to the LDL metabolism and development of atherosclerosis. Immune response to oxLDLs may exert a protective role at an early stage of atherosclerosis.
Increase in Oxidative Stress but Not in Antioxidant Capacity with Advancing Stages of Chronic Kidney Disease
Authors: Karamouzis Ioannis , Sarafidis Pantelis A. , Karamouzis Michael , Iliadis Stavros , Haidich Anna-Bettina , Sioulis Athanasios , Triantos Athanasios , Vavatsi-Christaki Norma , Grekas Dimitrios M.
Published: December 2007

Background/Aims: Increased oxidative stress in chronic kidney disease (CKD) was suggested to be both a cause and an effect of renal injury. However, the evolution of oxidant stress from early stages of renal function decline is not fully clear. This study aimed to determine the oxidant-antioxidant balance across the whole range of renal function. Methods: A total of 116 patients with CKD (85 predialysis patients divided into groups according to CKD stage, and 31 patients with end-stage renal disease (ESRD) on hemodialysis treatment), as well as 29 healthy subjects were evaluated. Plasma levels of 15-F2t-isoprostane (15-F2t-IsoP), a valid marker of oxidant stress, as well as total antioxidant capacity (TAC) and serum levels of vitamin E were measured in all participants. Results: Plasma 15-F2t-IsoP levels were higher in predialysis and ESRD patients compared to healthy subjects and were progressively increasing with advancing CKD stages (p < 0.001). In contrast, plasma TAC was similar between healthy subjects and predialysis patients, and presented a small reduction in ESRD patients (p < 0.001). Vitamin E levels were higher in healthy subjects compared to any other group (p < 0.001) and slightly higher in ESRD patients compared to predialysis patients (p < 0.01), but did not differ significantly between the groups of predialysis patients. Plasma 15-F2t-IsoP levels were inversely correlated with estimated glomerular filtration rate in predialysis patients (r = –0.65, p < 0.001). Conclusions: This study shows that 15-F2t-IsoP levels increase progressively with advancing CKD stages, whereas TAC and vitamin E levels remain rather stable with the loss of renal function and change only in patients with ESRD.
Tigecycline in vitro Activity against Gram-Negative and Gram-Positive Pathogens Collected in Italy
Authors: Roveta S. , Marchese A. , Debbia E.A.
Published: December 2007

Background: In this study (part of the global TEST program), the in vitro activity of tigecycline, a member of a new class of antimicrobial agents, the glycylcyclines, against clinical isolates collected in Italy was evaluated. Methods: A total of 200 clinical isolates were collected and identified in our institution during 2005. Minimum inhibitory concentrations (MICs) of the antimicrobial agents were determined by the broth microdilution method recommended by the CLSI in 2005. Results: Globally, 135 Gram-negative and 65 Gram-positive pathogens were evaluated. Tigecycline demonstrated excellent inhibitory activity against Acinetobacter spp., Haemophilus influenzae, Escherichia coli, Enterococcus spp., Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae with MIC90 ≤1 mg/l. Conclusion: Tigecycline exhibited potent in vitro antibacterial activity (comparable to or greater than most commonly employed antimicrobials) against both Gram-positive and Gram-negative clinical pathogens. These data suggest that tigecycline, with an expanded broad-spectrum antimicrobial activity, may be an effective empiric therapeutic option for the treatment of serious infections caused by clinically relevant pathogens.
Levofloxacin-Resistant Helicobacter pylori in Hong Kong
Authors: Lee Ching Ching , Lee Vivian W.Y. , Chan Francis K.L. , Ling Thomas K.W.
Published: December 2007

Background: Fluoroquinolone-resistant Helicobacter pylori emerged in 1995 and the resistance was due to point mutation in the gyrA gene. In this study we investigate the resistance mechanism and the antimicrobial susceptibilities of clarithromycin, metronidazole, amoxicillin, tetracycline and telithromycin against levofloxacin-resistant H. pylori in Hong Kong. Methods: One hundred and ninety-one nonduplicate H. pylori isolates were collected during 2004 and 2005, and 25 isolates with levofloxacin zone sizes less than 30 mm were selected for minimal inhibitory concentration determination by agar dilution, gyrA gene amplication and sequencing the amplified gyrA gene. Results: The prevalence of levofloxacin-resistant H. pylori was 11.5% (22/191). Among these levofloxacin-resistant strains, 7 (31.8%) and 10 (45.5%) were resistant to clarithromycin and metronidazole, respectively, 17 (77.3%) had point mutations in gyrA gene at amino acids 87, 91 and 130 and the most frequent mutation point was at position 91. Conclusions: Amoxicillin, tetracycline and telithromycin were active against levofloxacin-resistantH. pylori and levofloxacin resistance was mainly due to point mutation in the gyrA gene, especially at amino acid position 91.
Intracranial Hypotension from Intrathecal Baclofen Pump Insertion
Authors: Lad Shivanand P. , Li Gordon , Lin Shih-Chun , Henderson Jaimie M.
Published: December 2007

Intracranial hypotension is a syndrome of low cerebrospinal fluid pressure with a variable clinical presentation ranging from postural headaches to coma. A number of neuroradiologic techniques are now available to aid in the diagnosis of this syndrome (CT, MRI, radioisotope cisternography and CT myelography), each showing specific radiographic abnormalities. In this report, we present a case of intracranial hypotension secondary to baclofen pump placement. We review the major clinical findings, neuroimaging abnormalities, key diagnostic features as well as treatment options.
Successful Bilateral Subthalamic Nucleus Stimulation for Segmental Dystonia after Unilateral Pallidotomy
Authors: Novak Kevin E. , Nenonene Emmanuel K. , Bernstein Lawrence P. , Vergenz Sandra , Cozzens Jeffrey W. , Rezak Michael
Published: December 2007

Background: Several subcortical structures have been targeted for surgical treatment of dystonia, including motor thalamus, internal segment of globus pallidus (GPi), and more recently, the subthalamic nucleus (STN). Deep brain stimulation of GPi is currently the preferred surgical treatment, but it is unclear if targeting other structures would yield better results. Patients who have already had a pallidotomy yet continue to experience dystonic symptoms may be limited in further treatment options. Methods: A patient with medically intractable, segmental, early-onset, primary torsion dystonia presented for surgical consultation after exhausting nearly all treatment options. Medications, botulinum toxin injections, cervical denervation surgery, and left-sided pallidotomy failed to give adequate relief. The patient was implanted with STN stimulating leads bilaterally according to standard procedures. Results: The patient received a 36% improvement in dystonic symptoms as measured by several dystonia rating scales. These benefits persisted for 2 years after surgery despite several hardware-related complications, and the patient reported being very satisfied with the outcome. Conclusion: This result supports the efficacy of STN deep brain stimulation in dystonia patients, even those with prior pallidotomy.
Sex-Related Time-Dependent Variations in Post-Stroke Survival – Evidence of a Female Stroke Survival Advantage
Authors: Olsen Tom Skyhøj , Dehlendorff Christian , Andersen Klaus Kaae
Published: December 2007

Background: Women live longer than men, yet most studies show that gender has no influence on survival after stroke. Methods: A registry was started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, and it now holds 39,484 patients of which 48% are female. We studied the influence of gender on post-stroke mortality, from the time of admission through the subsequent years until death or censoring (mean follow-up time: 538 days). All patients underwent an evaluation including stroke severity, computed tomography and cardiovascular risk factors. Independent predictors of death were identified by means of a survival model based on 22,222 individuals with a complete data set. Results: Females were older and had severer stroke. Interestingly, the risk of death between genders was time dependent. The female/male stroke mortality rate favoured women from the first day of stroke and remained so during the first month suggesting a female survival advantage. Throughout the second month the rate reversed in favour of men suggesting that women in that period are paying a ‘toll’ for their initial survival advantage. Hereafter, the rate steadily decreased, and after 4 months women continued to have the same low risk as in the first week. Conclusions: Our study suggests a female superiority in stroke survival competence.
Effect of Serum Leptin Levels on Hypercapnic Ventilatory Response in Obstructive Sleep Apnea
Authors: Makinodan Kiyoshi , Yoshikawa Masanori , Fukuoka Atsuhiko , Tamaki Shinji , Koyama Noriko , Yamauchi Motoo , Tomoda Koichi , Hamada Kaoru , Kimura Hiroshi
Published: December 2007

Background: Leptin levels have been reported to be higher in patients with obstructive sleep apnea (OSA) than in control subjects with matching age and body mass index (BMI). Although animal studies have shown that leptin augments hypercapnic ventilatory response (HCVR), the effect of leptin on HCVR has not been clarified in OSA. Objectives: To investigate whether leptin could augment HCVR during wakefulness in patients with OSA. Methods: Of 134 consecutive patients with OSA, 13 eucapnic and 16 hypercapnic patients with OSA, and 12 control subjects matched for sex, age, and BMI were selected. Fasting serum leptin levels were collected, and HCVR during wakefulness assessed by the slope between minute ventilation and end-tidal PCO2. Results: There was a significant positive relationship between serum leptin levels and HCVR in the group including control subjects and eucapnic patients with OSA (r = 0.42, p < 0.05). Subgroup analyses suggest that serum leptin levels and HCVR were significantly higher in eucapnic patients with OSA than in control subjects. On the other hand, hypercapnic patients had lower HCVR than eucapnic patients (p < 0.05), whereas serum leptin levels were similar between the two OSA subgroups. Conclusion: Leptin levels and HCVR are correlated as long as the eucapnic condition is maintained. We speculate that a stimulating effect of leptin on HCVR may be masked by the hypoventilation state.
Diagnostic and Prognostic Utility of t(14;18) in Follicular Lymphoma
Authors: Deghiedy H. , Fouda M. , Shahin D. , Shamaa S. , El-Bedewy A. , Abd El-Ghaffar H.
Published: December 2007

Background: Follicular lymphoma (FL) is one of the most common non-Hodgkin’s lymphomas of B cells, being closely associated with a t(14;18) translocation. Detection of t(14;18), which is present in 70–95% of FL, might aid in FL diagnosis. Objective: To compare the efficacy of routine polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques in detecting t(14;18) in paraffin-embedded tissue samples of FL patients at different stages. Combined with other immunophenotypic biological determinants, detection of t(14;18) might help to determine patients at increased risk according to the FL International Prognostic Index (FLIPI) and therefore facilitate appropriate treatment. Design and Methods: This study was mainly based on a retrospective examination of formalin-fixed, paraffin-embedded lymph nodes. We selected fixed tissue samples of 21 FL patients treated at the National Cancer Institute Center in the period from 2000 to 2001. Results: FISH techniques could detect 14 of 18 FL cases with a sensitivity of 77.8%, while the PCR technique could detect only 11 of 18 FL cases with a sensitivity of 61.1%, resulting in a statistically significant difference between both techniques (p = 0.004). According to the FLIPI index, 9 of the 18 FL patients were categorized into the high-risk group (50%), 5 in the intermediated-risk group (27.8%) and 4 in the low-risk group (22.2%). Conclusion: The sensitivity of FISH is superior to that of PCR in the detection of the t(14;18) translocation in paraffin-embedded tissue samples. There is a statistically significant correlation between both CD10 and FISH with FLIPI.
Cyclosporin A Induces Peritoneal Fibrosis and Angiogenesis during Chronic Peritoneal Exposure to a Glucose-Based, Lactate-Buffered Dialysis Solution in the Rat
Authors: van Westrhenen Roos , Aten Jan , Hajji Najat , de Boer Onno J. , Kunne Cindy , de Waart Dirk R. , Krediet Raymond T.
Published: December 2007

Background/Aims: Cyclosporin A (CsA) stimulates the development of fibrosis. We investigated whether CsA contributes to peritoneal alterations induced by long-term exposure to dialysis solutions. Methods: Ten rats received peritoneal infusion of dialysis solution and oral CsA for 8 weeks. Eight received only the dialysis solution (controls). Peritoneal function was assessed at 8 weeks followed by sacrifice. The number of vessels was counted, fibrosis was assessed and hydroxyproline was determined. PCR was performed for vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β). Results: Histology revealed more fibrosis, hydroxyproline and vessels (thick walled) in CsA-exposed animals. Peritoneal transport was not different. The mRNA content of TGF-β, CTGF and VEGF was higher in CsA. Conclusion: CsA combined with exposure to dialysis solutions was associated with increased peritoneal fibrosis and angiogenesis.
Perseveration in Alzheimer’s Disease
Authors: Pekkala S. , Albert M.L. , Spiro III A. , Erkinjuntti T.
Published: December 2007

Background/Aims and Methods: Perseveration is common in Alzheimer’s disease (AD). We document the type and quantitative burden of perseveration as cognitive decline progresses from normal aging (n = 30) through mild AD (n = 20) to moderate AD (n = 20) by administering a semantic verbal fluency task. Results: We found perseveration to increase significantly with increasing severity of AD and different types of perseveration that distinguish the subject groups in a statistically significant manner. Recurrent and continuous perseverations appear early in AD. As the disease progresses in severity into moderate stage, the number of recurrent and continuous perseverations increases, and stuck-in-set perseverations emerge. Conclusion: The different types of perseveration are likely to reflect the progressive deterioration of different brain regions in AD.
Low CR1 (C3b Receptor) Level on Erythrocytes Is Associated with Poor Prognosis in Hemodialysis Patients
Authors: Ohi Hiroyuki , Tamano Mariko , Okada Noriko
Published: December 2007

Background: Erythropoietin in patients under dialysis treatment for renal failure is low which induces anemia. Treatment with recombinant erythropoietin (rEPO) has been used routinely as a supplement treatment for these patients. Immune complexes (IC) react with complement and bind to CR1 on erythrocytes (E-CR1), and are transported to the liver and/or spleen where IC removal and degradation occurs. The erythrocytes then return to circulation where they bind to additional IC. There are some patients whose E-CR1 expression is low with chronic anemia in spite of rEPO treatment. We hypothesized that in hemodialysis (HD) patients altered host defense against infection is associated with low levels of E-CR1. We examined if low E-CR1 in dialysis patients constitutes a risk factor for reduced host defense and poor outcome. Methods: In 95 HD patients, E-CR1 was quantified using a monoclonal E-CR1 antibody and FACS analysis followed by clinical course studies for 5 years. Results: The patients were divided into three groups by E-CR1 level. Percent survival for the low E-CR1 group (53.3%) was significantly lower than the high E-CR1 group (86.4%) (p < 0.01). There were more hepatitis C virus-positive patients within the low E-CR1 group (27.3%) than in the high E-CR1 group (4.7%) (p < 0.05). Furthermore, 10 patients with the lowest E-CR1 levels had severe complications, notably infection at an arteriovenous fistula. Conclusion: A reduced E-CR1 level might be a risk factor for reduced host defense and can be used as a predicting factor for poor prognosis in a HD patient.
Upregulation of the Release of Granulocyte-Macrophage Colony-Stimulating Factor from Keratinocytes Stimulated with Cysteine Protease Activity of Recombinant Major Mite Allergens, Der f 1 and Der p 1
Authors: Ogawa Takasuke , Takai Toshiro , Kato Takeshi , Kikuchi Yuko , Niyonsaba François , Ikeda Shigaku , Okumura Ko , Ogawa Hideoki
Published: December 2007

Background: Although exposure to mite allergens is an important risk factor for the production of IgE and is associated with various allergic diseases, there has been uncertainty as to the route of exposure by which sensitization occurs. Cystatin A is a skin-derived dominant inhibitor against proteolytic activity of major mite allergens, Der f 1 and Der p 1, and blocks the upregulation of IL-8 release from human keratinocytes stimulated with the allergens. We analyzed whether the stimulation of keratinocytes with the allergens upregulates the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), which has many actions relevant to allergic diseases including atopic dermatitis, and if so, whether cystatin A can block this process. Methods: Normal human keratinocytes and the human keratinocyte cell line HaCaT were stimulated with recombinant group 1 allergens in the absence or presence of cystatin A. Results: Stimulation with the recombinant allergens upregulated the release of GM-CSF from normal human keratinocytes in a culture with high calcium concentration and HaCaT cells, which could be inhibited by the addition of cystatin A. The allergens exhibiting proteolytic activity did not digest cystatin A. Proteolytic activity of recombinant Der f 1 was partially regenerated after incubation with keratinocytes even without preactivation by L-cysteine. Conclusion: Proteolytic activity of recombinant Der f 1 and Der p 1 upregulates GM-CSF and IL-8 release from keratinocytes in vitro, suggesting possible contributions to sensitization through the skin and the perpetuation of atopic dermatitis, as well as a homeostatic role for cystatin A against inflammation of the skin.
Genome-Wide Profiling of Antigen-Induced Time Course Expression Using Murine Models for Acute and Chronic Asthma
Authors: Park Seong Gyu , Choi Jung-Won , Kim Hyun jae , Roh Gu Seob , Bok Jeong , Go Min Jin , Kwack KyuBum , Oh Bermseok , Kim Yeonjung
Published: December 2007

Background: Asthma is a complex-trait disease caused by complicated interactions among multiple genetic and environmental risk factors. The clinical symptoms of asthma, such as periodic airway obstruction, hyperresponsiveness and mucus hypersecretion, are mediated by acute and chronic bronchial inflammation. Methods: To better understand the mechanisms by which allergen-induced acute inflammation leads to chronic asthma accompanied by irreversible airway remodeling, we analyzed time course transcriptional responses in the lungs of model mice that were exposed to aerosolized ovalbumin for up to 9 weeks after an initial sensitization. Results: We observed increased levels of total plasma IgE and histological changes in lung tissues from the ovalbumin-treated mice, which is consistent with the typical inflammatory phenotypes of asthma pathogenesis. Our oligonucleotide microarray analyses revealed a total of 776 differentially expressed genes induced by antigenic challenge (≧1.5-fold change, p < 0.05). Of these genes, most of the immune-responsive genes were transiently up-regulated in the early phase of the allergen treatment (within a week) with a concomitant up-regulation of genes involved in mucus production. These genes were not differentially regulated in the mice challenged for a longer period of time (up to 6 weeks). We also identified some of the genes implicated in extracellular matrix remodeling, for which the time course expression did not necessarily coincide with the expression patterns of immune-responsive genes. Conclusion: Our data suggest that there is a complex interregulatory genetic network associated with the structural changes that accompany the progression of the allergic inflammatory reaction in chronic asthma.
Neuropsychiatric Manifestations in Mild Cognitive Impairment: A Systematic Review of the Literature
Authors: Apostolova Liana G. , Cummings Jeffrey L.
Published: December 2007

Background: Mild cognitive impairment (MCI) is an etiologically heterogeneous condition that is characterized by cognitive changes without impairment of activities of daily living and insufficient to represent dementia. MCI is an important risk state for dementia. Neuropsychiatric symptoms may be present in MCI. Methods: We executed a PubMed search for articles on the neuropsychiatric manifestations in MCI and reviewed their findings. Results: Behavioral abnormalities are reported in 35–75% of MCI patients with the most common being depression, apathy, anxiety and irritability. The observed variability in symptom prevalence can be explained by the different sampling methods, MCI diagnostic criteria and behavioral instruments used. There is a compelling body of evidence that MCI patients with behavioral features are more prone to develop Alzheimer’s disease (AD) than patients without these features. Conclusions: Neuropsychiatric symptoms are common features of MCI. The behavioral changes observed in MCI are similar to those of AD and may help identify the subgroup of MCI patients with prodromal AD. Large prospective longitudinal studies would greatly contribute to our understanding of the epidemiology, diagnostic and prognostic value of the neuropsychiatric features in MCI.
Modulation of Network-Driven, GABA-Mediated Giant Depolarizing Potentials by SDF-1α in the Developing Hippocampus
Authors: Kasiyanov Alexander , Fujii Nobutaka , Tamamura Hirokazu , Xiong Huangui
Published: December 2007

Chemokine stromal cell-derived factor-1 (SDF-1, or CXCL12) plays an important role in brain development and functioning. Whole-cell patch clamp recordings were conducted on CA3 neurons in hippocampal slices prepared from neonatal rats between postnatal days 2 and 6 to study the modulatory effects of SDF-1α on network-driven, γ-aminobutyric-acid-mediated giant depolarizing potentials (GDPs), a hallmark of the developing hippocampus. We found that SDF-1α, the only natural ligand for chemokine CXC motif receptor 4 (CXCR4), decreased GDP firing without significant effects on neuronal passive membrane properties in neonatal hippocampal neurons. The SDF-1α-mediated decrease in GDP firing was blocked by T140, a CXCR4 receptor antagonist, suggesting that SDF-1α modulates GDP firing via CXCR4. We also showed that endogenous SDF-1 exerts a tonic inhibitory action on GDPs in the developing hippocampus. As SDF-1/CXCR4 are highly expressed in the developing brain and GDPs are involved in activity-dependent synapse formation and functioning, the inhibitory action of SDF-1α on GDPs may reflect a potential mechanism for chemokine regulation of neural development in early neonatal life.
Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo
Authors: Konrad Ildiko , Sauer Susanne , Orschiedt Lena , Koellnberger Maria , Lorenz Reinhard , Walter Ulrich , Massberg Steffen , Schulz Christian
Published: December 2007

Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8–12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by ∼50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8–12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.
Further validation and simplification of the Wells clinical decision rule in pulmonary embolism
Authors: Sohne Maaike , Kruip Marieke J. H. A , Tick Lidwine W , Gerdes Victor E , Bossuyt Patrick M , Wells Philip S , Buller Harry R , Gibson Nadine S ,   the Christopher study investigators
Published: December 2007

The Wells rule is a widely applied clinical decision rule in the diagnostic work-up of patients with suspected pulmonary embolism (PE).The objective of this study was to replicate, validate and possibly simplify this rule. We used data collected in 3,306 consecutive patients with clinically suspected PE to recalculate the odds ratios for the variables in the rule, to calculate the proportion of patients with PE in the probability categories, the area under the ROC curve and the incidence of venous thromboembolism during follow-up. We compared these measures with those for a modified and a simplified version of the decision rule. In the replication, the odds ratios in the logistic regression model were found to be lower for each of the seven individual variables (p=0.02) but the proportion of patients with PE in the probability categories in our study group were comparable to those in the original derivation and validation groups. The area under the ROC of the original, modified and simplified decision rule was similar: 0.74 (p=0.99; p=0.07).The venous thromboembolism incidence at three months in the group of patients with a Wells score ≤ 4 and a normal D-dimer was 0.5%, versus 0.3% with a modified rule and 0.5% with a simplified rule. The proportion of patients safely excluded for PE was 32%, versus 31% and 30%, respectively. This study further validates the diagnostic utility of theWells rule and indicates that the scoring system can be simplified to one point for each variable.
Peroxisome proliferator-activated receptor γ and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles
Authors: Spinelli Sherry L , Pollock Stephen J , Murant Thomas I , O’Brien Jamie J , Blumberg Neil , Francis Charles W , Taubman Mark B , Ray Denise M , Phipps Richard P
Published: December 2007

Peroxisome proliferator-activated receptor γ (PPARγ) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPARγ and that PPARγ ligands blunt platelet activation. To further understand the nature of PPARγ in platelets, we determined the platelet PPARγ isoform(s) and investigated the fate of PPARγ following platelet activation. Our studies demonstrated that human platelets contain only the PPARγ1 isoform and after activation with thrombin, TRAP, ADP or collagen PPARγ is released from internal stores. PPARγ release was blocked by a cytoskeleton inhibitor, Latrunculin A. Platelet-released PPARγ was complexed with the retinoid X receptor (RXR) and retained its ability to bind DNA. Interestingly, the released PPARγ and RXR were microparticle associated and the released PPARγ/RXR complex retained DNA-binding ability. Additionally, a monocytic cell line, THP-1, is capable of internalizing PMPs. Further investigation following treatment of these cells with the PPARγ agonist, rosiglitazone and PMPs revealed a possible transcellular mechanism to attenuate THP-1 activation. These new findings are the first to demonstrate transcription factor release from platelets, revealing the complex spectrum of proteins expressed and expelled from platelets, and suggests that platelet PPARγ has an undiscovered role in human biology.