bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative Bacterial/Fungal Infections: A Challenging Problem in Critically Ill Patients after Abdominal Surgery
Authors: Lichtenstern C. , Schmidt J. , Knaebel H.P. , Martin E. , Büchler M.W. , Weigand M.A.
Published: January 2007

Critically ill patients after extended surgical procedures are at high risk for postoperative infections. The overall incidence of sepsis increased constantly over the last decade, whereas sepsis-related mortality decreased, due to new intensive care options. After extended intra-abdominal surgery the abdomen is the predominant focus of sepsis, followed by respiratory tract infections. Unspecific clinical signs lead to the diagnosis of postoperative sepsis. Early focus identification by clinical, laboratory and radiologic examination is of major importance for a promising therapy, followed by immediately initiated procedures for source control and an adequate anti-infective drug therapy. For nosocomial sepsis, the use of antimicrobial regimens with extended spectra and potent activity against both Gram-negative and Gram-positive bacterial pathogens are warranted. Fungal infections play a great role for immunocompromized patients, e.g. after solid organ transplantation or under chronic corticoid therapy. An increasing incidence of multi-drug resistance in bacterial and fungal isolates has been observed in the last years. This is becoming a growing problem also for critically ill patients after abdominal surgery. Standardized treatment protocols including supportive and adjunctive therapy and the use of modern anti-infective agents may lead to a decrease in postoperative mortality due to sepsis.
Clinical Outcomes of Tubal Heterotopic Pregnancy: Assisted vs. Spontaneous Conceptions
Authors: Han Sang Hoon , Jee Byung Chul , Suh Chang Suk , Kim Seok Hyun , Choi Young Min , Kim Jung Gu , Moon Shin Yong
Published: January 2007

Background: It has not been established whether the clinical outcomes of tubal heterotopic pregnancy resulting from assisted conception are different to those of spontaneous conception. The aim of this study was to compare the clinical course and the outcome of intrauterine gestation following surgical treatment for tubal heterotopic pregnancy according to the method of pregnancy. Methods: Medical records of 13 cases of tubal heterotopic pregnancy experienced in Seoul National University Hospital during 1990–2004 and 30 case reports of tubal heterotopic pregnancy published in the Korean Journal of Obstetrics and Gynecology during 1980–2004 were reviewed retrospectively. The clinical outcomes were compared between the assisted (n = 23) and spontaneous conception groups (n = 20). Results: The assisted conception group had a significantly higher preoperative systolic blood pressure and a previous history of pelvic pathology. The spontaneous group had a higher incidence of tubal rupture and hemoperitoneum. The assisted conception group had a higher live birth rate than the spontaneous group (47.8 vs. 20%, p = 0.056). Conclusions: In tubal heterotopic pregnancy, the assisted conception group had a more favorable clinical course and intrauterine gestation outcome following surgical treatment when compared with the spontaneous conception group.
Short-Term Pathophysiologic Changes and Histopathologic Findings of the Auditory Pathway after Closed Head Injury, Using a Rabbit Model
Authors: Danielidis Vasilios , Tsimpiris Nikolaos , Balatsouras Dimitrios G. , Polychronidis Alexandros , Perente Sabach , Papadopoulos Nikolaos , Ypsilantis Petros , Simopoulos Constantinos
Published: January 2007

Hearing impairment is a well-known consequence of closed head injury (CHI). The aim of this study was to elucidate the pathogenesis of CHI-induced hearing loss, using a rabbit model. Twelve New Zealand white rabbits were divided into two groups of 6. In the first group, CHI was induced mechanically, whereas the rabbits of the second group served as controls. Baseline distortion product otoacoustic emissions (DPOAEs), contralateral suppression (CS) of the DPOAEs and auditory brainstem response (ABR) were obtained. The same measurements were performed in the first group after CHI. Three hours later, the animals were sacrificed and their brain was excised and subjected to histopathologic examination. Mean I–III ABR latencies were increased and DPOAE amplitudes and CS values were reduced in the trauma group after CHI, at a statistically significant level. Histopathologic examination of the temporal lobe and brainstem showed multiple hemorrhagic and necrotic areas, with edema in the surrounding region. The vestibulocochlear nerve was severely damaged at its emerging site at the brainstem. In conclusion, both peripheral and central involvement of the auditory pathway was found after CHI. Otoacoustic emissions in conjunction with ABR may provide significant information on both peripheral and central auditory function.
Effects of a Single High Dose of Cisplatin on the Melanocytes of the Stria Vascularis in the Guinea Pig
Authors: Laurell Göran , Ekborn Andreas , Viberg Agneta , Canlon Barbara
Published: January 2007

The antineoplastic drug cisplatin is known to cause a reduction in endocochlear potential. The hypothesis to be tested was whether a single high dose of cisplatin affects the melanocytes by altering the expression of melanin. Pigmented guinea pigs received a bolus injection of cisplatin (8 mg/kg as a 15-second intravenous infusion). Auditory brainstem response (ABR) thresholds and morphological analysis of the hair cells and the stria vascularis were made 96 h after injection. ABR thresholds were elevated (15–40 dB) at 12–30 kHz and a significant loss of outer hair cells in the more basal regions was found. Cisplatin caused a significantly lower density of melanin in the intermediate cells in the basal region without any signs of apoptosis. Changes in melanin content were not noted in the middle or apical cochlear regions. Significant correlations were found between melanin density, ABR threshold shifts and outer hair cell loss in the region corresponding to 30 kHz. The findings reported here further support the multiple cytotoxic effect of cisplatin on the inner ear.
Enterovirus, Cytomegalovirus, and Epstein-Barr Virus Infection Screening in Idiopathic Sudden Sensorineural Hearing Loss
Authors: Gross Menachem , Wolf Dana G. , Elidan Josef , Eliashar Ron
Published: January 2007

Sudden sensorineural hearing loss (SSNHL) is frequently classified as ‘idiopathic’ since the causative factor is not identified in most cases. In the present study we determined whether SSNHL is associated with common viral infections, namely enterovirus, cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Between April 2004 and March 2005, we conducted a prospective cohort study on 48 unselected patients with unilateral idiopathic SSNHL. Plasma samples obtained at presentation were analyzed for the presence of enterovirus RNA by reverse-transcription polymerase chain reaction (RT-PCR). Recent occurrence of CMV and EBV infection was determined by serological tests. Among 23 men and 25 women aged 18–84 years (mean age 51.67 years), none presented with clinical symptoms of a viral infection compatible with preceding or concurrent viral infection. One patient (2.08%) had evidence of enterovirus infection by RT-PCR, 3 patients (6.25%) had EBV IgM, and none were positive for CMV IgM. The majority of SSNHL patients (91.67%) did not have evidence of any of the three common viral infections upon presentation. The present study failed to identify recent or concurrent systemic viral infections among SSNHL patients, except for a small proportion who demonstrated recent viral infection. Therefore the theory that viral infection is a factor in SSNHL pathogenesis is not supported by this study. Further studies in larger patient populations and different epidemiological settings are required in order to verify the true role of viral infections in SSNHL.
Impact of Alcohol on Vestibular Function in Relation to the Legal Limit of 0.25 mg/l Breath Alcohol Concentration
Authors: Chiang Hou-Hsien , Young Yi-Ho
Published: January 2007

The aim of this study was to investigate the effect of alcohol on sacculocollic and vestibulo-ocular reflex systems, when the breath alcohol concentration (BrAC) is close to the legal limit of 0.25 mg/l. Twenty healthy male volunteers underwent vestibular evoked myogenic potential and caloric coupled with visual suppression tests. These tests were conducted prior to imbibing alcohol at a dosage of 0.5 g/kg to achieve a peak BrAC of around 0.25 mg/l. Once the peak BrAC was reached, these tests were performed again. Predosing and postdosing analytical results were compared, as were those with BrAC levels ≧ 0.25 mg/l and <0.25 mg/l. After ingesting alcohol, 36 ears (90%) showed vestibular evoked myogenic potential responses, with a significantly increased latency of peak p13. The mean slow-phase velocity of caloric nystagmus in 40 ears after dosing was significantly reduced, and that with BrAC ≧0.25 mg/l was significantly less than that with BrAC <0.25 mg/l. Likewise, the visual suppression index decreased considerably after alcohol ingestion. In conclusion, from the perspective of vestibular function, the 0.25-mg/l BrAC limit gains clinical significance, because the vestibulo-ocular reflex performance deteriorates further, when the BrAC exceeds 0.25 mg/l. However, impaired performance of sacculocollic reflex and vestibulocerebellar interaction has occurred, when the BrAC was <0.25 mg/l, suggesting that a lower legal threshold is appropriate.
Genomic Damage and Malignancy in End-Stage Renal Failure: Do Advanced Glycation End Products Contribute?
Authors: Šebeková Katarína , Wagner Zoltán , Schupp Nicole , Boor Peter
Published: January 2007

In end-stage renal disease (ESRD) there is not only excessive morbidity and mortality due to cardiovascular disease but also an enhanced occurrence of various types of cancer. Both are characterized by oxidative stress and inflammation as two of the central underlying causes of the disease states. In cancer, genomic damage has been demonstrated to be of high pathogenetic relevance. DNA lesions may induce mutations of oncogenes and tumor-suppressor genes which, in the long-run, may lead to malignancies if mutagenicity is not mitigated by repair mechanisms. A high incidence of genomic damage in ESRD patients has been validated by various biomarkers of DNA lesions. We reviewed the mechanisms of DNA damage, focusing in particular on the role of advanced glycation end products (AGEs) which accumulate markedly in renal insufficiency. Considering the in vitro and in vivo findings to date, one has to assume a significant role of AGEs in DNA damage and the potential development of cancer.
Prevention and Treatment of Dementia or Alzheimer’s Disease by Statins: A Meta-Analysis
Authors: Zhou Bin , Teramukai Satoshi , Fukushima Masanori
Published: January 2007

Background/Aim: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are thought to reduce the amount of Abeta peptides by reducing cholesterol from blood and/or cerebrospinal fluid. We performed this meta-analysis to evaluate the preventive and treatment effects of statins on dementia and Alzheimer disease onset. Methods: Relevant studies were systematically identified, and data were abstracted according to predefined criteria. We used a fixed-effects model and a random-effects model to compute pooled relative risks and to assess statistical heterogeneity. Results: The pooled crude odds ratios in statin users as compared with nonusers were 0.67 (95% confidence interval CI 0.54–0.82) in the dementia group and 0.81 (95% CI 0.64–1.02) in the Alzheimer group. The pooled adjusted relative risks calculated by random-effects model were 0.77 (95% CI 0.45–1.30) in the dementia group and 0.81 (95% CI 0.56–1.16) in the Alzheimer group. Conclusions: Statin use did not show a beneficial effect on the risk of dementia or Alzheimer’s disease. Further study and independent confirmation of the association between statin use and dementia and Alzheimer’s disease in larger clinical trials are warranted.
The Public’s Perception of the Plausibility of Dementia Risk Factors Is Not Influenced by Scientific Evidence
Authors: Low Lee-Fay , Anstey Kaarin Jane
Published: January 2007

Background/Aim: The public know little about risk factors for dementia. The aim of this study was to explore belief structures underlying how plausible risk factors for dementia appear to the general public. Methods: Two thousand members of the Australian public were surveyed by telephone on their beliefs regarding dementia risk factors. Factor analysis was performed on 17 modifiable behaviours that were rated by participants as increasing, not changing or decreasing the risk of dementia. Results: Three factors were obtained – Health and Lifestyle, Activity, and Nutrition. Items loading on the Health and Lifestyle factor were management of cardiovascular risk factors, drinking more water, reducing stress, coffee and tea, and alcohol intake. Items loading on the Activity factor were mental, physical and social activity and getting out and about more. Items loading on the Nutrition factor were eating foods high in omega-3 fatty acids, antioxidants and estrogen, using non-aluminium cookware and taking vitamin and nutritional supplements. Factors were characterised by similarity of items, rather than level of scientific evidence of an association with dementia. Factor scale scores differed according to sociodemographic characteristics. Conclusions: The public do not process dementia risk factor information based on level of scientific evidence.
Gamma Knife Radiosurgery Targeting Protocols for the Experiments with Small Animals
Authors: Tokumaru Osamu , Hayashi Motohiro , Katayama Yoko , Tomida Mihoko , Kawakami Yoriko , Kouyama Nobuo
Published: January 2007

Background/Aims: Manipulation of brain functions via Gamma Knife (GK) irradiation would have numerous applications in clinical and experimental neurology. Methods: Alteration of brain functions in the unilaterally irradiated striatum was indexed through monitoring freely moving rat behaviors. Spontaneous activity and rotations on the apomorphine test, which can detect dopaminergic function imbalance, were indexed employing our behavior tracking system. The spatial distribution of necrotic lesions was explored using serial sections, and was assumed to represent the real foci of the GK target. Results: Distinct behavioral alterations corresponded to the precise locations of the lesions in various areas of the basal ganglia. Displacement of the irradiation sites in the anteromedial direction increased spontaneous activity, and posterolateral shift provoked circling behavior on the apomorphine test. Conclusion: Accurate positioning of the target is crucial for experimental GK irradiation locally focused on domains of a small brain such as that of the rat. Here, we propose a protocol for converting the ‘intended’ focus, based on brain map coordinates, to a ‘planned’ focus on the MR imaging coordinate system with the Régis-Valliccioni stereotactic frame.
Long-Term Evaluation of Treatment of Chronic, Therapeutically Refractory Tinnitus by Neurostimulation
Authors: Bartels H. , Staal M.J. , Holm A.F. , Mooij J.J.A. , Albers F.W.J.
Published: January 2007

Objective: Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by means of chronic electrical stimulation of the vestibulocochlear nerve. Patients: Inclusion criteria were severe, chronic, therapeutically refractory, unilateral tinnitus and severe hearing loss at the ipsilateral site. Out of 6 patients, 4 patients were selected for long-term evaluation. Two patients were not evaluated because of premature dropout. Material and Methods: A stimulation electrode was placed around the vestibulocochlear nerve through a retrosigmoid approach and connected to a subcutaneously positioned pulse generator via an extension cable. Follow-up was performed 3 months and 42.5 months after implantation. Three measures for treatment outcome were used. First, effect sizes were determined by means of the total Tinnitus Handicap Inventory (THI) score using Cohen’s formula. Second, general and tinnitus-specific audiometric tests were performed in on and off conditions of the neurostimulation system. Third, recordings were noted for tinnitus severity and treatment success on a visual analogue scale. Results: All 4 patients reported successful treatment with neurostimulation. The effect size after 3 months was 0.7, indicating an average effect, while the effect size measured during long-term follow-up was 1.75, indicating a substantial effect with major clinical implications. No changes in hearing level for both ears were measured. The neurostimulation system did not change the tinnitus pitch in any of the patients, and resulted in a minimal reduction of tinnitus loudness in only 2 patients. In all 4 patients the original tinnitus sound was replaced by another, pleasantly perceived sound. The average VAS score of perceived tinnitus severity was reduced from 8 to 3.25. The average VAS score for treatment success was 7.25. Conclusions: The long-term follow-up of neurostimulation treatment for chronic tinnitus shows promising results. Long-term results were better than those determined after a 3-month follow-up. In all patients the tinnitus was replaced by another sound, which was perceived as pleasant. Further studies are needed before accepting neurostimulation as a treatment modality for chronic, therapeutically refractory tinnitus.
Neuroanatomical Localization of the ‘Precentral Knob’ with Computed Tomography Imaging
Authors: Park Michael C. , Goldman Marc A. , Park Min J. , Friehs Gerhard M.
Published: January 2007

Background/Aims: The ‘precentral knob’, a cortical representation of the motor hand function, can be identified and localized consistently using magnetic resonance imaging (MRI) and functional MRI. We present a method of indirectly identifying and localizing the Ω-shaped precentral knob using the anatomical landmarks on computed tomography (CT). Methods: CT and MRI obtained within 24 h from 10 patients undergoing a headache workup and found to be negative for any anatomical abnormalities were studied. First, the precentral knob was identified in the CT images. Then, the ‘coronal suture line’ and ‘midline’ were identified and used to measure the distance to the precentral knob on both hemispheres. MRI was used to confirm the location of the precentral knob in the CT images based on anatomical landmarks (i.e. sulcal configurations). Results: The precentral knob is located 45.1 ± 5.2 mm posterior with respect to the coronal suture line and 33.9 ± 3.4 mm lateral to the midline on the right hemisphere, and 44.6 ± 5.7 mm posterior and 33.2 ± 2.5 mm lateral on the left hemisphere. Conclusion: We present a method of consistently identifying and localizing the Ω-shaped precentral knob, a cortical representation of the motor hand function, using CT.
Subthalamic Nucleus Stimulation in Parkinson’s Disease Patients Intolerant to Levodopa
Authors: Lyons Kelly E. , Davis Justin T. , Pahwa Rajesh
Published: January 2007

Levodopa responsiveness has been shown to be the best predictor of improvement after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson’s disease (PD). The objective of this study was to assess the effect of STN DBS on PD patients intolerant to levodopa due to severe acute side effects such as intolerable nausea. There were 10 patients in the study who received STN DBS for PD. Five patients who were intolerant to levodopa were matched based on age, disease duration, sex and presurgical disease severity to 5 patients taking levodopa and demonstrating a good levodopa response. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale activities of daily living and motor subscales as well as tremor, rigidity and bradykinesia scores at 3, 6 and 12 months after surgery compared to baseline, and these improvements were equivalent between the two groups. Patient global ratings also indicated significant improvements at all follow-up visits. There were no differences in stimulator settings between the two groups at the 3-, 6- or 12-month follow-up visits. In conclusion, although levodopa responsiveness is the best predictor for outcome after STN DBS, carefully selected PD patients intolerant to levodopa can have significant improvement.
Serum Levels of Calcification Inhibition Proteins and Coronary Artery Calcium Score: Comparison between Transplantation and Dialysis
Authors: Mazzaferro Sandro , Pasquali Marzia , Pugliese Francesco , Barresi Giusi , Carbone Iacopo , Francone Marco , Sardella Daniela , Taggi Franco
Published: January 2007

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 ± 12 years; 30 males, 21 females; previous D duration 4.8 ± 4.2 years; Tx since 6.6 ± 5.5 years; Cr 1.8 ± 0.6 mg/dl) and in 49 D patients (age 49 ± 14 years; 30 males,19 females; D duration 5.6 ± 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 ± 1,637 vs. 1,311 ± 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: rs = 0.439, p < 0.001, and rs = 0.510, p < 0.0001; D: rs = 0.471, p < 0.001, and rs = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (rs = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (rs = –0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (rm = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (rm = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.
Low Plasma RANTES Levels Are an Independent Predictor of Cardiac Mortality in Patients Referred for Coronary Angiography
Authors: Cavusoglu Erdal , Eng Calvin , Chopra Vineet , Clark Luther T. , Pinsky David J. , Marmur Jonathan D.
Published: January 2007

Objective—Our objective was to evaluate the prognostic value of baseline plasma RANTES levels in patients with known or suspected coronary artery disease. RANTES is a chemokine produced by a variety of cell types including platelets that has been implicated in atherosclerosis.

Methods and Results—Baseline plasma RANTES levels were measured in 389 male patients undergoing coronary angiography at a Veterans Affairs Medical Center. The patients were followed-up prospectively for the occurrence of cardiac mortality and myocardial infarction. Follow-up data at 24 months were available for 97% of patients. In the entire cohort of patients, low baseline RANTES levels were an independent predictor of cardiac mortality. For cardiac death at 24 months, the survival rate was 87.3% in the lowest tertile of RANTES values, compared with 94% in the upper 2 tertiles combined (P=0.0298 by log rank test). Furthermore, when patients were risk-stratified into those with and without an acute coronary syndrome, RANTES was an independent predictor of both cardiac mortality and myocardial infarction in those without an acute coronary syndrome. Finally, RANTES was also an independent predictor of cardiac mortality in the diabetic subset.

Conclusions—In a cohort of male patients undergoing coronary angiography, low baseline plasma RANTES levels are an independent predictor of cardiac mortality.
A Diet-Induced Hypercholesterolemic Murine Model to Study Atherogenesis Without Obesity and Metabolic Syndrome
Authors: Hartvigsen Karsten , Binder Christoph J. , Hansen Lotte F. , Rafia Apaïs , Juliano Joseph , Hörkkö Sohvi , Steinberg Daniel , Palinski Wulf , Witztum Joseph L. , Li Andrew C.
Published: January 2007

Objective—

Western-type high-fat/high-cholesterol diets used to induce atherogenesis in low-density lipoprotein (LDL) receptor-deficient mice also lead to obesity with concomitant metabolic complications, eg, hypertriglyceridemia, hyperinsulinemia, and insulin resistance. Our aim was to design a diet inducing atherosclerosis through moderate hypercholesterolemia without associated parameters of the metabolic syndrome.

Methods and Results—

Male LDL receptor-deficient mice were fed regular chow (RC; 0.01% cholesterol/4.4% fat), cholesterol-enriched regular chow (HC; 1% cholesterol/4.4% fat), or Western diet (WD 0.06% cholesterol/21% milk fat) for 28 weeks. HC-feeding led to elevated plasma (≈20.7 mmol/L [800 mg/dL]) and LDL cholesterol and accelerated atherosclerosis. Plasma triglycerides were unaffected. Compared with RC-fed controls, HC-fed mice had normal body weight gain and normal fasting levels of glucose, free fatty acids, and insulin. In contrast, WD-fed mice were extremely hypercholesterolemic (>41.4 mmol/L), obese, hypertriglyceridemic, hyperinsulinemic, insulin resistant, and showed adverse health such as skin/fur abnormalities and hepatic steatosis. Although atherosclerotic surface areas in the entire aorta were similar in HC-fed and WD-fed mice, lesions in aortic origin cross sections were significantly larger in WD-fed mice. However, morphology was similar in lesions of equal size.

Conclusions—

The HC diet induced moderate hypercholesterolemia and extensive atherosclerosis and should be useful to study specific aspects of atherogenesis in the absence of confounding effects of the metabolic syndrome.
IAP Survivin Regulates Atherosclerotic Macrophage Survival
Authors: Blanc-Brude Olivier P. , Teissier Elisabeth , Castier Yves , Lesèche Guy , Bijnens Ann-Pascal , Daemen Mat , Staels Bart , Mallat Ziad , Tedgui Alain
Published: January 2007

Objectives—

Inflammatory macrophage apoptosis is critical to atherosclerotic plaque formation, but its mechanisms remain enigmatic. We hypothesized that inhibitor of apoptosis protein (IAP) survivin regulates macrophage death in atherosclerosis.

Methods and Results—

Western blot analysis revealed discrete survivin expression in human aorta lipid streaks but virtually none in advanced atherosclerotic plaques, despite increased XIAP and cIAP2 levels. Survivin was detected in CD68-positive macrophages infiltrating human lipid streaks by immunohistochemistry. In advanced atherosclerotic plaques, only rare macrophages outside the necrotic core or occasional fibrous cap smooth muscle cells expressed survivin. In vitro, macrophage colony-stimulating factor-stimulated mouse macrophage survivin expression, proliferation and resistance to apoptosis. Conversely, prolonged oxidized low-density lipoprotein treatment abolished macrophage survivin expression and triggered apoptosis after 12 hours, despite enhanced XIAP and cIAP2 expression. Adenoviral overexpression of survivin conferred macrophages with sustained resistance to apoptosis after oxidized low-density lipoprotein, tumor necrosis factor-α, or staurosporine challenge.

Conclusions—

Survivin is a critical modulator of atherosclerotic macrophage apoptosis under dual control by growth factors and oxidized lipids accumulating in atheroma. In early lipid streaks, growth factor-stimulated survivin expression may contribute to macrophage accumulation and survival, but dysregulation of survivin expression caused by recurrent oxidized low-density lipoprotein exposure may favor apoptosis in advanced atherosclerotic plaques, despite upregulated cIAP2 and XIAP.
Critical Role for Casein Kinase 2 and Phosphoinositide-3-Kinase in the Interferon-γ–Induced Expression of Monocyte Chemoattractant Protein-1 and Other Key Genes Implicated in Atherosclerosis
Authors: Harvey Elizabeth J. , Li Na , Ramji Dipak P.
Published: January 2007

Objective—The interferon-γ (IFN-γ)–mediated regulation of macrophage gene expression is of crucial importance in the pathogenesis of atherosclerosis. The mechanisms underlying the actions of IFN-γ signaling in macrophages were investigated using monocyte chemoattractant protein (MCP)-1 as a model gene.

Methods and Results—The IFN-γ–induced expression of MCP-1 in macrophages was attenuated by inhibitors of phosphoinositide-3-kinase (PI3K), casein kinase 2 (CK2), and Janus kinase (JAK)-2. AKT was the downstream target for PI3K action. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that signal transducer and activator of transcription (STAT)-1 interacted with IFN-γ responsive elements in the MCP-1 gene promoter. The IFN-γ–induced activity of the MCP-1 gene promoter and an artificial promoter containing STAT1 responsive elements was inhibited by expression of dominant negative forms of JAK-1 and -2, STAT1, CK2, and AKT. The action of CK2 and AKT on STAT1 activation was mediated, at least in part, through the regulation of serine 727 phosphorylation. Analysis of a number of other genes regulated by this cytokine and implicated in atherosclerosis revealed a gene-specific action for PI3K/AKT in IFN-γ signaling.

Conclusions—These studies provide novel insights into the role of PI3K/AKT and CK2 in IFN-γ signaling relevant to changes in macrophage gene expression during atherosclerosis.
Axl/Phosphatidylinositol 3-Kinase Signaling Inhibits Mineral Deposition by Vascular Smooth Muscle Cells
Authors: Collett Georgina D.M. , Sage Andrew P. , Kirton John Paul , Alexander M. Yvonne , Gilmore Andrew P. , Canfield Ann E.
Published: January 2007

The calcification of blood vessels correlates with increased morbidity and mortality in patients with atherosclerosis, diabetes, and end-stage kidney disease. The receptor tyrosine kinase Axl is emerging as an important regulator of adult mammalian physiology and pathology. This study tests the hypothesis that Axl prevents the deposition of a calcified matrix by vascular smooth muscle cells (VSMCs) and that this occurs via the phosphatidylinositol 3-kinase (PI3K) signaling pathway. First, we demonstrate that Axl is expressed and phosphorylated in confluent VSMCs and that its expression is markedly downregulated as these cells calcify their matrix. Second, we demonstrate that overexpression of wild-type Axl, using recombinant adenoviruses, enhances Axl phosphorylation and downstream signaling via PI3K and Akt. Furthermore, overexpression of Axl significantly inhibits mineral deposition by VSMCs, as assessed by alizarin red staining and
45
Ca accumulation. Third, the addition of a PI3K inhibitor, wortmannin, negates the inhibition of mineralization by overexpression of wild-type Axl, suggesting that activation of downstream signaling via PI3K is crucial for its inhibitory activity. In contrast, Axl-mediated signaling is not enhanced by overexpression of kinase-dead Axl and mineralization is accelerated, although β-glycerophosphate is still required for this effect. Finally, the caspase inhibitor zVAD.fmk attenuates the increased mineralization induced by kinase-dead Axl, suggesting that kinase-dead Axl stimulates mineralization by inhibiting the antiapoptotic effect of endogenous Axl. Together, these results demonstrate that signaling through Axl inhibits vascular calcification in vitro and suggest that therapeutics targeting this receptor may open up new avenues for the prevention of vascular calcification in vivo.
Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion
Authors: Wagner Charlotte , de Wit Cor , Kurtz Lisa , Grünberger Christian , Kurtz Armin , Schweda Frank
Published: January 2007

Renin secretion and synthesis in renal juxtaglomerular cells are controlled by short feed back loops involving angiotensin II and the intrarenal blood pressure. The operating mechanisms of these negative feed back regulators are widely unknown, except for the fact that both require calcium to exert their inhibitory action. We here show that in the absence of connexin40 (Cx40), which form gap junctions between juxtaglomerular and endothelial cells, the negative control of renin secretion and synthesis by angiotensin II and by intravasal pressure is abrogated, while the regulation by salt intake and β-adrenergic stimulation is maintained. Renin secretion from Cx40-deficient kidneys or wild-type kidneys treated with the nonselective gap junction blocker 18α-glycyrrhetinic acid (10 μmol/L) resembles the situation in wild-type kidneys in the absence of extracellular calcium. This disturbed regulation is reflected by an enhanced plasma renin concentration despite an elevated blood pressure in Cx40-deficient mice. These findings indicate that Cx40 connexins and likely intercellular communication via Cx40-dependent gap junctions mediate the calcium-dependent inhibitor effects of angiotensin II and of intrarenal pressure on renin secretion and synthesis. Because Cx40 gap junctions are also formed between renin producing cells and endothelial cells our finding could provide additional information to suggest that the endothelium may be strongly involved in the control of the renin system.
Translational Induction of VEGF Internal Ribosome Entry Site Elements During the Early Response to Ischemic Stress
Authors: Bornes Stéphanie , Prado-Lourenco Leonel , Bastide Amandine , Zanibellato Catherine , Iacovoni Jason S. , Lacazette Eric , Prats Anne-Catherine , Touriol Christian , Prats Hervé
Published: January 2007

Vascular endothelial growth factor-A (VEGF), a powerful factor involved in vasculogenesis and angiogenesis, is translationally regulated through 2 independent internal ribosome entry sites (IRESs A and B). IRESs enable an mRNA to be translated under conditions in which 5′-cap–dependent translation is inhibited, such as low oxygen stress. In the VEGF mRNA, IRES A influences translation at the canonical AUG codon, whereas the 5′ IRES B element regulates initiation at an upstream, in frame CUG. In this study, we have developed transgenic mice expressing reporter genes under the control of these 2 IRESs. We reveal that although these IRESs display low activity in embryos and adult tissues, they permit efficient translation at early time points in ischemic muscle, a stress under which cap-dependent translation is inhibited. These results demonstrate the in vivo efficacy of the VEGF IRESs in response to a local environmental stress such as hypoxia.
Absence of the G Protein–Coupled Receptor G2A in Mice Promotes Monocyte/Endothelial Interactions in Aorta
Authors: Bolick David T. , Whetzel Angela M. , Skaflen Marcus , Deem Tracy L. , Lee Jianyi , Hedrick Catherine C.
Published: January 2007

The G protein–coupled receptor G2A is highly expressed on macrophages and lymphocytes and has been localized to atherosclerotic plaques. We examined the role of G2A in modulating monocyte/endothelial interactions in the vessel wall. We measured adhesion of WEHI 78/24 monocytes to aortas of C57BL/6 (B6) and G2A-deficient (G2A
−/−
) mice using an ex vivo adhesion assay. G2A
−/−
mice had 10-fold elevations in adhesion of monocytes to aortas. Injection of GFP-expressing wild-type macrophages into B6 and G2A
−/−
mice in vivo showed increased macrophage accumulation in the aortic wall of G2A
−/−
mice. We isolated aortic endothelial cells (ECs) from B6 and G2A
−/−
mice and found a 2-fold increase in intercellular adhesion molecule-1 and E-selectin surface expression on G2A
−/−
ECs using flow cytometry. Using ELISA, we found a 3-fold increase in interleukin-6 and monocyte chemoattractant protein-1 production by G2A
−/−
ECs compared with B6 ECs. We found a dramatic increase in nuclear localization of the p65 subunit of nuclear factor κB in G2A
−/−
ECs. Transfection of G2A into G2A
−/−
ECs to restore normal expression levels reduced p65 nuclear localization to 35%. Restoration of G2A expression in G2A
−/−
ECs significantly reduced intercellular adhesion molecule-1 and endothelial selectin surface expression and reduced monocyte chemoattractant protein-1 and interleukin-6 production. Restoring G2A to G2A
−/−
ECs reduced monocyte adhesion by 80% compared with G2A
−/−
ECs in a flow chamber assay. Absence of G2A in endothelium results in proinflammatory signaling and increased monocyte/endothelial interactions in the aortic wall. Thus, endothelial G2A expression may aid in prevention of vascular inflammation and atherosclerosis.
Active Finger Extension
Authors: Smania Nicola , Paolucci Stefano , Tinazzi Michele , Borghero Anna , Manganotti Paolo , Fiaschi Antonio , Moretto Giuseppe , Bovi Paolo , Gambarin Mattia
Published: January 2007

Background and Purpose—

Early prognosis of arm recovery is a major clinical issue in stroke. The aim of this study was to assess the prognostic value of 4 simple bedside tests.

Methods—

Forty-eight patients with arm paresis/plegia were evaluated on days 7, 14, 30, 90 and 180 after stroke. Assessment included 4 potential predictors of arm recovery (active finger extension, shoulder abduction, shoulder shrug and hand movement scales) and 3 outcome measures evaluating arm function (Nine Hole Peg Test, Fugl-Meyer arm subtest, Motricity Index arm subtest).

Results—

The active finger extension scale was the most powerful prognostic factor. Patients with active finger extension scores >3 had a high probability of achieving good performance as assessed by the Motricity Index.

Conclusions—

Active finger extension is a reliable early predictor of recovery of arm function in stroke patients.
Effect of Measurement on Sex Difference in Stroke Mortality
Authors: Sheikh Kazim , Bullock Claudia M.
Published: January 2007

The 1994 to 1997 administrative data on 40 450 elderly Medicare beneficiaries and general population of 2 states were used to measure “case mortality” (deaths attributable to any cause among cases of acute stroke), “case fatality” (deaths caused by cerebrovascular diseases among cases of acute stroke), and “population mortality” (deaths caused by stroke in the elderly general population). Mortality was higher in men than in women according to all measures except population mortality caused by subarachnoid hemorrhage. There was no sex difference in 1-year case fatality. One-year all-cause mortality among cases of nonhemorrhagic stroke or all types of stroke was higher in men than in women. Similar sex differences were found in 4-year population mortality caused by nonhemorrhagic stroke or all types of stroke combined. The 3 measures differed with respect to sex difference in stroke mortality. How stroke is defined and how mortality is measured does affect sex difference.
Cerebral Fat Microembolism and Cognitive Decline After Hip and Knee Replacement
Authors: Koch Sebastian , Forteza Alejandro , Lavernia Carlos , Romano Jose G. , Campo-Bustillo Iszet , Campo Nelly , Gold Stuart
Published: January 2007

Background and Purpose—

Intra-operative cerebral microembolism may be a factor in the etiology of cognitive decline after orthopedic surgery. We here examine the impact of intra-operative microembolism on cognitive dysfunction after hip and knee replacement surgery.

Methods—

We enrolled 24 patients, at least 65 years old, requiring elective knee or hip replacement surgery. A transcranial Doppler shunt study was done to determine study eligibility so that the final study population consisted of 12 consecutive patients with and 12 consecutive patients without a venous-arterial shunt. A standard neuropsychological test battery was administered before surgery, at hospital discharge and 3 months after surgery. All patients were monitored intra-operatively for microemboli. Quality of life data were assessed at 1 year.

Results—

The mean age of patients was 74 years. All patients had intra-operative microemboli. The mean number of emboli was 9.9±18. Cognitive decline was present in 18/22 (75%) at discharge and in 10/22 (45%) at 3 months, despite improved quality of life measures. There was no correlation between cognitive decline and intra-operative microembolism.

Conclusion—

Cognitive decline was seen frequently after hip and knee surgery. Intra-operative microembolism occurred universally but did not significantly influence postoperative cognition. Quality of life and functional outcome demonstrated improvement in all cases in spite of cognitive dysfunction.
Central Periodic Breathing During Sleep in Acute Ischemic Stroke
Authors: Hermann Dirk M. , Siccoli Massimiliano , Kirov Philip , Gugger Matthias , Bassetti Claudio L.
Published: January 2007

Background and Purpose—

It has been suggested that central periodic breathing during sleep (CPBS) may develop in unilateral supratentorial stroke without cardiopulmonary disease and disturbed consciousness. Not many data existed about such patients.

Methods—

Of 31 patients with first-ever stroke, we report 3 patients with CPBS in the absence of cardiopulmonary and vigilance disturbances. Patient assessments included polysomnography, MRI and echocardiography. Nocturnal breathing was reassessed after 1 to 3 months.

Results—

The patients had ischemic strokes in the left cingulate cortex, left insula and right paramedian thalamus. They were fully conscious when submitted to sleep recordings and lacked overt cardiovascular dysfunctions (ejection fractions=67%, 48%, 65%). CPBS was present during 18% to 24% of sleep. In all patients, breathing improved during stroke recovery.

Conclusions—

CPBS may be present in strokes involving autonomic (insula) and volitional (cingulate cortex, thalamus) respiratory networks. As such, CPBS partly resolves within weeks.
High-Density Lipoprotein Cholesterol
Authors: Sanossian Nerses , Saver Jeffrey L. , Navab Mohamad , Ovbiagele Bruce
Published: January 2007

Background and Purpose—

This review characterizes the current state of knowledge of high-density lipoprotein (HDL) in relation to stroke.

Summary of Review—

HDL has anti-atherosclerotic and anti-inflammatory properties and is an important component in atherosclerosis. Serum HDL-cholesterol levels are inversely related to heart disease and stroke risk. There are various established and experimental treatments which can raise serum HDL cholesterol and improve its function.

Conclusion—

HDL is an emerging target for atherosclerotic stroke treatment with the potential to dramatically impact the care of stroke patients.
The Tension between Fire Risk and Carbon Storage: Evaluating U.S. Carbon and Fire Management Strategies through Ecosystem Models
Authors: Girod C. M. , Hurtt G. C. , Frolking S. , Aber J. D. , King A. W.
Published: January 2007

Fire risk and carbon storage are related environmental issues because fire reduction results in carbon storage through the buildup of woody vegetation, and stored carbon is a fuel for fires. The sustainability of the U.S. carbon sink and the extent of fire activity in the next 100 yr depend in part on the type and effectiveness of fire reduction employed. Previous studies have bracketed the range of dynamics from continued fire reduction to the complete failure of fire reduction activities. To improve these estimates, it is necessary to explicitly account for fire reduction in terrestrial models. A new fire reduction submodel that estimates the spatiotemporal pattern of reduction across the United States was developed using gridded data on biomass, climate, land-use, population, and economic factors. To the authors’ knowledge, it is the first large-scale, gridded fire model that explicitly accounts for fire reduction. The model was calibrated to 1° × 1° burned area statistics [Global Burnt Area 2000 Project (GBA-2000)] and compared favorably to three important diagnostics. The model was then implemented in a spatially explicit ecosystem model and used to analyze 1620 scenarios of future fire risk and fire reduction strategies. Under scenarios of climate change and urbanization, burned area and carbon emissions both increased in scenarios where fire reduction efforts were not adjusted to match new patterns of fire risk. Fuel reducing management strategies reduced burned area and fire risk, but also limited carbon storage. These results suggest that to promote carbon storage and minimize fire risk in the future, fire reduction efforts will need to be increased and spatially adjusted and will need to employ a mixture of fuel-reducing and non-fuel-reducing strategies.
Sensitivity of Simulated Boreal Fire Dynamics to Uncertainties in Climate Drivers
Authors: Rupp T. Scott , Chen Xi , Olson Mark , McGuire A. David
Published: January 2007

Projected climatic warming has direct implications for future disturbance regimes, particularly fire-dominated ecosystems at high latitudes, where climate warming is expected to be most dramatic. It is important to ascertain the potential range of climate change impacts on terrestrial ecosystems, which is relevant to making projections of the response of the Earth system and to decisions by policymakers and land managers. Computer simulation models that explicitly model climate–fire relationships represent an important research tool for understanding and projecting future relationships. Retrospective model analyses of ecological models are important for evaluating how to effectively couple ecological models of fire dynamics with climate system models. This paper uses a transient landscape-level model of vegetation dynamics, Alaskan Frame-based Ecosystem Code (ALFRESCO), to evaluate the influence of different driving datasets of climate on simulation results. Our analysis included the use of climate data based on first-order weather station observations from the Climate Research Unit (CRU), a statistical reanalysis from the NCEP–NCAR reanalysis project (NCEP), and the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5). Model simulations of annual area burned for Alaska and western Canada were compared to historical fire activity (1950–2000). ALFRESCO was only able to generate reasonable simulation results when driven by the CRU climate data. Simulations driven by the NCEP and MM5 climate data produced almost no annual area burned because of substantially colder and wetter growing seasons (May–September) in comparison with the CRU climate data. The results of this study identify the importance of conducting retrospective analyses prior to coupling ecological models of fire dynamics with climate system models. The authors’ suggestion is to develop coupling methodologies that involve the use of anomalies from future climate model simulations to alter the climate data of more trusted historical climate datasets.