bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral Microbleeds Are Independently Associated with Arterial Stiffness in Stroke Patients
Authors: Seo Woo-Keun , Lee Jong-Moon , Park Moon Ho , Park Kun Woo , Lee Dae Hie
Published: November 2008

Background: Cerebral microbleeds (CMB) are now receiving considerable attention for their association with stroke recurrence and white matter lesions (WML). Pulse wave velocity (PWV), which is a measure of arterial stiffness, was found to be one of the predictors of cardiovascular disease and stroke in a large population-based study. The current study set out to investigate the association between CMB and arterial stiffness. Methods: Subjects included 255 patients with strokes, such as cerebral infarctions or transient ischemic attacks, who were enrolled at Korea University Stroke Registry, Ansan arm, between October 2005 and May 2007, and underwent MRI and PWV. CMB, stroke lesion, stroke subtype and WML were coded by researchers blind to clinical details. Arterial stiffness was assessed by measuring brachial-ankle PWV (baPWV). Results: CMB were observed in 57 patients (22.4%), and were most frequently seen in the basal ganglia, followed by the cerebral cortex. The baPWV was significantly higher in patients with CMBs compared to those without (p < 0.01). After adjustment for demographics, vascular risk factors and hemodynamic parameters, baPWV proved to be significantly associated with CMB using a logistic regression test (odds ratio 1.119, 95% CI 1.013–1.237). Conclusions: PWV had an independent association with CMB in patients with stroke. These findings suggest that arterial stiffness may be pathophysiologically associated with CMB.
Noninvasive Depiction of the Lenticulostriate Arteries with Time-of-Flight MR Angiography at 7.0 T
Authors: Hendrikse Jeroen , Zwanenburg Jaco J. , Visser Fredy , Takahara Taro , Luijten Peter
Published: November 2008

Objective: The lenticulostriate arteries (LSAs) are small penetrating branches which are feeding the basal ganglia. Thus far, no noninvasive imaging method has been capable of visualizing the LSAs. We explore the possibilities of three-dimensional time-of-flight (TOF) MR angiography (MRA) at 7 T to visualize the LSAs. Subjects and Methods: We included 10 healthy volunteers (age range, 19–46 years; 4 men, 6 women). TOF MRA was performed on a 7.0-tesla ultra-high-field MR system equipped with a volume transmit and 16-channel receive head coil. Images were acquired with a 0.6-mm isotropic resolution with a scan time of 9 min and 33 s. The mean length and number of LSAs (with standard deviations) were evaluated on coronal and sagittal maximum intensity projections of the axial source data set. Results: The mean total number of LSAs (± standard deviation) visualized on the left and right side combined was 7.0 ± 1.8. Per side, the average number of visualized LSAs was 3.5 ± 1.1, and the maximum number of visualized LSAs was 5. The mean length of the visualized LSAs was 23 ± 6.6 mm. The most laterally visualized LSAs showed the longest length (29 ± 5.0 mm), with a stepwise decrease in length for the more medially visualized LSAs. Conclusion: We show the ability of TOF MRA at 7.0 T to image the LSAs. Direct imaging of these LSAs in clinical studies may increase the understanding of the pathophysiology of brain tissue changes, such as lacunar infarcts, which are thought to be caused by small-vessel disease.
Misdiagnosis of Transient Ischemic Attacks in the Emergency Room
Authors: Prabhakaran Shyam , Silver Adam J. , Warrior Lakshmi , McClenathan Bethany , Lee Vivien H.
Published: November 2008

Background: To determine a pattern of symptoms and/or risk factors that distinguishes transient ischemic attack (TIA) from nonischemic causes of transient neurologic attacks (NI-TNA). Methods: We reviewed demographic, clinical, and hospital data on 100 consecutive patients with transient focal neurologic episode(s) lasting less than 24 h and in whom the initial diagnosis was TIA. After inpatient evaluation and review, final diagnoses were made by two stroke neurologists. Using stepwise multivariable logistic regression, we estimated odds ratios (OR) for independent predictors of NI-TNA. p < 0.05 was considered significant. Results: Of the 100 patients, 40 were confirmed to have TIA and 60 NI-TNA. Compared to TIA patients, those with NI-TNA were less likely to be male and white but more likely to have a history of prior unexplained TNA, gradual symptom onset, associated nonspecific symptoms, longer symptom duration, and delayed presentation. Other variables were similar between the two groups. In a multivariable logistic regression model, gradual symptom onset (adjusted OR 6.7, p = 0.002), prior history of unexplained transient neurologic attack (adjusted OR 10.6, p = 0.031), and presence of nonspecific symptoms (adjusted OR 4.2, p = 0.008) were independent predictors of the final diagnosis of NI-TNA. Conclusions: Distinguishing TIA from nonischemic causes is difficult in the emergency room, with 60% of suspected TIA patients having nonischemic causes on inpatient evaluation. We found 3 clinical features that may be useful in the emergency room triage of transient neurologic attacks. Further study is needed to develop tools that can accurately diagnose TIA.
Plasma Levels of Asymmetric Dimethylarginine in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarct and Leukoencephalopathy
Authors: Rufa Alessandra , Blardi Patrizia , De Lalla Arianna , Cevenini Gabriele , De Stefano Nicola , Zicari Enza , Auteri Alberto , Federico Antonio , Dotti Maria Teresa
Published: November 2008

Background: Asymmetric dimethylarginine (ADMA) is a marker of endothelial dysfunction and a new independent risk factor for adverse cerebrovascular events in small vessel disease. Conversely, L-arginine (LARG) may have a protective role. Methods: To assess ADMA, LARG levels and LARG/ADMA ratio in 16 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and normal controls, and to look for possible correlations with white matter changes. Plasma levels of ADMA and LARG were assayed by high-performance liquid chromatography in all subjects. The overall T1 and T2 lesion load was obtained from brain MRI of patients with CADASIL. Results: ADMA plasma concentrations (1.5 ± 2.0 µM) were significantly higher (p < 0.05) in CADASIL patients than in controls (0.35 ± 0.075 µM). Analyzing only CADASIL subjects, an inverse borderline-significant correlation was found between LARG/ADMA (190 ± 20) and T2-weighted lesion volumes (57.9 ± 46.5; r = –0.578, p = 0.024). Conclusion: Our results may indicate the possible coexistence of endothelial dysfunction in CADASIL patients, broadening the range of potentially pathogenetic mechanisms in this disease and providing insights for future therapeutic strategies.
Heparin-Induced Thrombocytopenia: A Serious Complication of Heparin Therapy for Acute Stroke
Authors: Kawano Hiroyuki , Toyoda Kazunori , Miyata Shigeki , Yamamoto Haruko , Okamoto Akira , Kakutani Isami , Walenga Jeanine M. , Naritomi Hiroaki , Minematsu Kazuo
Published: November 2008

Background: Despite the lack of supporting evidence, unfractionated heparin (UFH) is frequently given to acute ischemic stroke patients. This study was designed to determine the incidence of heparin-induced thrombocytopenia (HIT) during acute stroke and to elucidate the clinical features of stroke patients with HIT. Methods: Of 1,078 consecutive patients with acute ischemic stroke, 392 were given intravenous UFH. Ten of these developed prominent thrombocytopenia without any other underlying etiology; they were suspected of having HIT. These 10 patients were studied retrospectively. The clinical diagnosis of HIT was made according to two published scoring systems. Antiplatelet factor 4/heparin antibodies in the plasma were detected by the enzyme-linked immunosorbent assay (ELISA) and were confirmed by the 14C-serotonin release assay. Results: Eight patients met the criteria for clinical HIT according to both scoring systems. Of these, serological tests were positive in 2 patients only on ELISA and in 2 patients on both assays. The amount of UFH given was greater in the 4 patients with positive serological findings than in the others (p = 0.043). Three patients developed further thromboembolic events, including 1 patient who developed possible cancer-associated thrombosis. Two patients were dead and the remaining 6 patients were dependent at the time of hospital discharge. The clinical severity and outcome of these patients were relatively unfavorable compared to other acute patients. Conclusions: The prevalence of HIT was 0.5% based on both the clinical scoring systems and serological assays. Monitoring for HIT should be included in the medical management of stroke to avoid further complications.
Transcranial Ultrasound from Diagnosis to Early Stroke Treatment
Authors: Hölscher Thilo , Schlachetzki Felix , Zimmermann Markus , Jakob Wolfgang , Ittner Karl Peter , Haslberger Johann , Bogdahn Ulrich , Boy Sandra
Published: November 2008

Background: To test whether portable duplex ultrasound devices can be used in a prehospital ‘911’ emergency situation to assess intracranial arteries. Methods: Non-contrast-enhanced transcranial duplex ultrasound studies were performed either immediately at the site of the emergency (i.e. private home) or after transfer into the emergency helicopter/ambulance vehicle. Results: A total of 25 patients were enrolled. In 5/25 cases, intracranial vessels could not be visualized due to insufficient quality of the temporal bone window. In 20/25 cases, bilateral visualization and Doppler flow measurements of the middle cerebral artery could be assessed in a mean time less than 2 min. Conclusion: Emergency assessment of intracranial arteries using portable duplex ultrasound devices is feasible shortly after arrival at the patient’s site.
Fructosamine Levels and Hyperglycemia in Preterm Neonates
Authors: Gyarmati Judit , Tokes-Fuzesi Margit , Kovacs Gabor L. , Gaal Valeria , Vida Gabriella , Ertl Tibor
Published: November 2008

Background: Hyperglycemia is a common complication of prematurity, which requires attention because of its high prevalence and multiple consequences. Serum fructosamine used in diabetic patients provides information about the average glucose concentration in the preceding period of 2–3 weeks. Objective: We investigated the physiologic characteristics of a glycemic marker, fructosamine, in preterm and term neonates. We also studied its association with hyperglycemia and related morbidities of preterm infants. Method: Fructosamine levels of 22 extremely premature (gestational age, GA: 25.8 ± 1.0 weeks), 36 moderately premature (GA: 29.8 ± 1.3 weeks) and 26 term infants (GA: 39.1 ± 1.3 weeks) were determined in the 1st week of life. Fructosamine assay was repeated in all preterm neonates in the 4th and 7th postnatal weeks. Hyperglycemic episodes and main morbidities of preterm infants were recorded and analyzed in association with fructosamine levels. Results: Preterm infants had higher fructosamine levels after birth compared to term infants and a postnatal fall was observed. Serum fructosamine did not show association with the occurrence of hyperglycemia or its main morbidities in preterm infants. Conclusion: In the framework of our study, we could not confirm the usefulness of fructosamine determination in the glycemic control of preterm neonates during the perinatal period.
Cot-Side Electro-Encephalography and Interstitial Glucose Monitoring during Insulin-Induced Hypoglycaemia in Newborn Lambs
Authors: Harris Deborah L. , Battin Malcolm R. , Williams Chris E. , Weston Philip J. , Harding Jane E.
Published: November 2008

Background: The optimal approach to detection and management of neonatal hypoglycaemia remains unclear. Objectives: We sought to demonstrate whether electro-encephalography (EEG) changes could be detected on the amplitude-integrated EEG monitor during induced hypoglycaemia in newborn lambs, and also to determine the accuracy of continuously measured interstitial glucose in this situation. Methods: Needle electrodes were placed in the P3-P4, O1-O2 montages. The interstitial glucose sensor was placed subcutaneously. After 30 min baseline recordings, hypoglycaemia was induced by insulin infusion and blood glucose levels were monitored every 5 min. The infusion was adjusted to reduce blood glucose levels by 0.5 mmol/l every 15 min and then maintain a blood glucose level <1.0 mmol/l for 4 h. EEG parameters analysed included amplitude, continuity and spectral edge frequency. The interstitial and blood glucose levels were compared. Results: All lambs (n = 15, aged 3–11 days) became hypoglycaemic, with median blood glucose levels falling from 6.5 to 1.0 mmol/l, p < 0.0001. There were no detectable changes in any of the measured EEG parameters related to hypoglycaemia, although seizures occurred in 2 lambs. There was moderate agreement between the intermittent blood glucose and continuous interstitial glucose measurements in the baseline, decline, and hypoglycaemia periods (mean difference –0.7 mmol/l, 95% confidence interval, CI, –2.8 to 1.4 mmol/l). However, agreement was poor during reversal of hypoglycaemia (mean difference 4.5 mmol/l, 95% CI –1.1 to 10.7 mmol/l). Conclusions: The cot-side EEG may not be a useful clinical tool in the detection of neurological changes induced by hypoglycaemia. However, continuous interstitial glucose monitoring may be useful in the management of babies at risk of hypoglycaemia.
‘Time Is a GIFT in GIST’ – The Medical and Paramedical Perspective of a Case with Metastatic Gastrointestinal Stromal Tumor
Authors: Sevinc Alper , Camci Celalettin
Published: November 2008

Few recent developments in oncology have generated comparable interest as have the dramatic successes in the therapy of gastrointestinal stromal tumors (GIST) with imatinib mesylate. Imatinib, a selective tyrosine kinase inhibitor, is currently the standard of care first-line treatment for unresectable or metastatic GIST, improving survival time and delaying disease progression. The authors report a 50-year-old male patient referred as relapsed chemotherapy-resistant CD117– leiomyosarcoma. After learning about the failure of chemotherapy, the patient became depressive and considered committing a suicide. We performed a second CD117 staining. As the second analysis was found to be positive, the diagnosis of leiomyosarcoma was changed to GIST. Imatinib 600 mg/day was started. The result with imatinib was appraised as a partial response/stable disease after the chemotherapy failure. The patient‘s depressive mood was also improved after imatinib. The medical and paramedical perspectives of the case are presented to emphasize the importance of immunohistochemical staining and its inhibition by a novel tyrosine kinase inhibitor in GIST. All nonepithelial tumors, particularly nonepithelial abdominal tumors of leiomyoblastic appearance should be considered to be GIST unless an experienced pathologist who does CD117 staining routinely confirms a different diagnosis. Interestingly, depression due to chemotherapy failure was also alleviated with imatinib. According to a recent study, median time to progression was 24 months, and overall survival was 57 months, reaching 5 years with imatinib. Conclusion: time is a GIFT in GIST.
The Role of Oxidative Mechanisms in the Etiopathogenesis of Pterygium: A Preliminary Study
Authors: Uçakhan Ömür Ö. , Kanpolat Ayfer , Elgün Serenay , Durak İlker
Published: November 2008

Background: To evaluate the role of light-induced oxidative mechanisms in the pathogenesis of primary pterygium. Methods: Pterygium specimens were obtained from 18 eyes of 18 patients undergoing pterygial removal (group A), and normal conjunctival specimens were obtained from 18 eyes of 18 patients undergoing cataract surgery (group B). In all specimens, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities were studied and compared. Results: In group A, the mean SOD activity was lower, and the mean MDA level was higher when compared to group B. However, these differences did not reach clinical significance (p > 0.05). On the other hand, the mean CAT activity was statistically significantly higher in group A when compared to controls (p = 0.017). Conclusion: This preliminary study indicates that oxidative mechanisms seem to play a role in the pathogenesis of pterygium. These mechanisms are apparently activated by ultraviolet irradiation. Further studies are required to establish the role of oxidative mechanisms in the pathogenesis of primary or recurrent pterygia.
Primary Carcinoids of the Liver: A Review of Symptoms, Diagnosis and Treatments
Authors: Gravante Gianpiero , De Liguori Carino Nicola , Overton John , Manzia Tommaso Maria , Orlando Giuseppe
Published: November 2008

Introduction: To elucidate the clinical presentation, diagnosis and management of primary hepatic carcinoid tumours, a literature search was conducted and summarized. Materials and Methods: Published primary hepatic carcinoid tumour case reports and series were searched and selected in the Medline, EMBASE and Cochrane Library databases. Results: Sixty-nine cases meeting the inclusion criteria were identified. Twenty-eight patients were male (28/69 = 40.6%). The median age at diagnosis was 50 years (range 8–83 years). The most common presentation described was abdominal pain (23/69 = 33.3%), or no symptoms at all (16/69 = 23.2%). Symptoms of carcinoid syndrome were described in 18.9% of cases (13/69). The most frequently secreted hormones were gastrin (7/69 = 10.1%) and chromogranin A. In 31.9% of patients (22/69), surgical treatment was not adopted. Of those treated surgically, 63.8% underwent a hepatic resection (44/69) and 4.3% a liver transplantation (3/69). After a median follow-up of 31 months (range 0–180 months), 39.1% of patients (27/69) died and 52.2% (36/69) survived. Conclusions: Primary hepatic carcinoids are an important entity in which the exclusion of different primary locations is necessary. When feasible, hepatic resection is the treatment of choice. Liver transplantation has been described in a small number of unresectable cases.
Presence and Extent of Cardiac Magnetic Resonance Microvascular Obstruction in Reperfused Non-ST-Elevated Myocardial Infarction and Correlation with Infarct Size and Myocardial Enzyme Release
Authors: Mewton N. , Bonnefoy E. , Revel D. , Ovize M. , Kirkorian G. , Croisille P.
Published: November 2008

Objective: Microvascular obstruction (MO) is a factor of adverse outcome in patients with ST-elevated myocardial infarction (STEMI). We assessed the presence and extent of MO and its relationship with infarct size and left ventricular (LV) functional parameters after acute non-ST-elevated myocardial infarction (NSTEMI). Methods: Twenty-five patients with first acute NSTEMI underwent a cine and first-pass perfusion cardiac magnetic resonance (CMR) study, with late gadolinium enhancement imaging 72 h after myocardial infarction. Results: MO was detected in 32% of patients, and its extent comprised 0.5–3.1% of the total LV mass (mean 1.9 ± 1.2%). Patients with MO had a significantly larger infarct size than patients without (14.1 ± 5.9 vs. 5.3 ± 4.1% LV mass; p < 0.001). There was no significant difference between both groups for the LV functional parameters and LV ejection fraction (58.5 ± 6.8 vs. 62.6 ± 9.6%; p = 0.29). Patients with MO showed a higher troponin I release (570 ± 364 vs. 148 ± 103 IU; p = 0.003) and a higher creatine kinase release (29,887 ± 18,263 vs. 10,287 ± 5,283 IU; p = 0.007). Conclusions: In patients with acute NSTEMI, MO has a frequency similar to that observed in patients with STEMI and also correlates with the infarct extent. The prognostic significance on clinical outcome remains to be shown in this specific population.
Donepezil Treatment of Severe Alzheimer’s Disease in Nursing Home Settings. A Responder Analysis
Authors: Jelic Vesna , Haglund Anders , Kowalski Jan , Langworth Sven , Winblad Bengt
Published: November 2008

Background/Aims: Our objective was to define clinically meaningful outcomes in donepezil versus placebo treatment in severe Alzheimer’s disease (AD) and to describe characteristics of responders. Methods: Analyses were performed on data from a 6-month, double-blind, parallel-group, placebo-controlled study on the efficacy of donepezil in 248 nursing home residents. Various individual responses were defined as stabilisation or improvement on the Severe Impairment Battery (SIB), Alzheimer’s Disease Cooperative Study-activities of daily living scale (ADCS-ADL), Mini-Mental State Examination, Neuropsychiatric Inventory (NPI) or Clinical Global Impression of Improvement. Three composite measures were defined by combining the individual response criteria on these outcomes. The impact of baseline disease severity and of concomitant use of psychotropic drugs was also analysed. Results: At 6 months, greater proportions of patients defined as responders to donepezil on individual efficacy measures showed significant stabilisation or improvement compared with placebo on the SIB (≧0, ≧4 or ≧7 points) and Mini-Mental State Examination (≧0 or ≧3 points), and positive trends on the ADCS-ADL-severe (≧3 points) and the NPI cluster based on mood items. All 3 composite measures of efficacy showed a significantly higher proportion of responders in the donepezil group. The responders had a similar distribution between the 2 subgroups of cognitive and functional disease severity at baseline. The donepezil-treated patients taking psychotropic drugs showed significantly greater improvement on the SIB, less deterioration on the ADCS-ADL, and had higher Clinical Global Impression of Improvement scores and a trend towards lower NPI scores. The baseline demographic and clinical profile did not differ between the non-responders and responders on the composite outcome measures. Conclusion: The results demonstrate that donepezil treatment of patients with severe AD consistently shows stabilisation or improvement across multiple outcome measures in individual patients, including cognitive, functional and behavioural symptoms.
Neural Correlates of Caregiver Burden in Cortical Basal Syndrome and Frontotemporal Dementia
Authors: Knutson K.M. , Zamboni G. , Tierney M.C. , Grafman J.
Published: November 2008

Aims: To determine areas of atrophy in patients that are associated with caregiver burden. Methods: We measured caregiver burden, dementia and neuropsychiatric scores in 22 patients with corticobasal syndrome (CBS) and 25 with frontotemporal dementia (FTD), and in 14 healthy controls. We used voxel-based morphometry to correlate caregiver burden with gray matter loss. Results: Increased dementia and behavioral disturbances contributed to higher burden scores in CBS patients, while behavioral disturbances alone significantly affected burden scores in frontal-variant FTD (FTD-fv) patients. In CBS patients, caregiver burden scores correlated with atrophy in left inferior and middle temporal gyri. Conclusions: Caregivers of FTD-fv patients had significantly higher burden scores than caregivers of CBS patients. Damage to areas important in semantic knowledge appears critical in increased burden for CBS caregivers.
Predictive Role of BNP and NT-proBNP in Hemodialysis Patients
Authors: Sun Linlin , Sun Yan , Zhao Xuezhi , Xu Chenggang , Chen Dongping , Li Lin , Ma Yiyi , Rong Shu , Mei Changlin
Published: November 2008

Background: Cardiovascular events (CVE) are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. These patients are often excluded from CV clinical trials, and the prognostic factors associated with CVE in patients with ESRD have not been fully explored. We investigated the role of BNP and NT-proBNP in predicting the outcome and prognostic value in hemodialysis with ESRD patients. Methods: Baseline NT-proBNP and BNP, indices of dialysis adequacy, and biochemical characteristics were assessed in 217 dialysis patients with ESRD who were followed prospectively for 2 years or until death. CVE included cardiovascular death, myocardial infarction, heart failure and stroke. Results: Using multivariable Cox regression analysis, BNP and NT-proBNP remained predictive of cardiovascular mortality (BNP: hazard ratio 1.22, 95% confidence interval (CI) 1.21–11.04, p < 0.05; NT-proBNP hazard ratio 1.86, 95% CI 1.14–9.36, p < 0.05), fatal/nonfatal CHF (BNP: 1.35, 1.33–11.78, p < 0.05; NT-proBNP: 2.25, 1.54–12.68, p < 0.001) and fatal/nonfatal MI (BNP: 0.61, 2.38–19.53, p = 0.42; NT-proBNP: 1.90, 3.28–20.17, p < 0.001). NT-proBNP had better predictive value than BNP for mortality (area under the ROC curve (AUC) 0.83 vs. 0.61; p < 0.05). Conclusion: These data showed that BNP and NT-proBNP are very sensitive and specific predictors of CVE in dialysis patients.
A Randomized Trial of Low-Animal-Protein or High-Fiber Diets for Secondary Prevention of Calcium Nephrolithiasis
Authors: Dussol Bertrand , Iovanna Cecilia , Rotily Michel , Morange Sophie , Leonetti Françoise , Dupuy Patricia , Vazi Alain , Saveanu Adriana , Loundou Anderson , Berland Yvon
Published: November 2008

Background: The purpose of this trial was to evaluate the efficacy of a low-animal-protein diet (LAPD) or a high-fiber diet (HFD) for the prevention of calcium nephrolithiasis recurrence. Methods: We conducted a 4-year randomized trial comparing the effect of 2 diets in 175 idiopathic calcium stone formers. Fifty-five were assigned to a LAPD (<13% of total energy derived from protein), 60 were assigned to a HFD (>25 g/day fiber) and 60 were placed on a normal diet (control group). The primary outcome measure was the time to the first recurrence of calcium nephrolithiasis. Daily urine compositions were analyzed at baseline, at month 4 (M4), M12, M24, M36 and M48. Results: Seventy-three patients completed the trial (23 in the LAPD group, 27 in the HFD group and 23 in the control group). Recurrence was 48% (11/23) in the LAPD group, 63% (17/27) in the HFD group and 48% (11/23) in the control group (p = not significant). During follow-up, urinary calcium levels and other urine parameters did not change significantly in the 3 groups, except for a significant decrease in 24-hour urinary sulfate in the LAPD group. Conclusions: In idiopathic calcium stone formers, neither a LAPD nor a HFD appeared to provide protection against recurrence.
Mechanisms behind the Synergistic Effect of Sirolimus and Imatinib in Preventing Restenosis after Intimal Injury
Authors: Tigerstedt Nina-Maria , Aavik Einari , Lehti Satu , Hayry Pekka , Savolainen-Peltonen Hanna
Published: November 2008

Background: We have shown that the combination of sirolimus and imatinib synergistically inhibits denudation-induced neointimal hyperplasia in rats. We have now dissected the mechanisms behind this synergy and evaluated its long-term efficacy. Methods: After aortic denudation injury, rats received established submaximal doses of sirolimus (1.0 mg/kg/day), imatinib (10.0 mg/kg/day), the combination of these, or vehicle per os from 3 days before the operation until 14 days after injury. Vessel histology and complete blood counts were monitored until 90 days after injury. Neointimal cell outgrowth, migration and proliferation were evaluated in ex vivo vessel cultures. Quantitative real-time polymerase chain reaction and immunohistochemistry were used for gene and protein expression analysis. Results: The combination therapy caused a synergistic decrease in the number of neointimal nuclei and area throughout the observation period. It also prevented postinjury thrombocytosis and leukocytosis, and almost abolished neointimal cell outgrowth and migration. Furthermore, the combination therapy resulted in upregulation of smooth muscle cell (SMC) markers SM22α and cysteine and glycine-rich protein 2, and of the anti-apoptotic BCL2 mRNA. Conclusions: Combination therapy confers superior long-term vasculoprotection, possibly by inhibition of postoperative thrombocytosis and leukocytosis, inhibition of neointimal cell migration to the injury site and maintenance of cell integrity by inhibition of apoptosis and SMC dedifferentiation.
Mechanism of ATP-Induced Local and Conducted Vasomotor Responses in Isolated Rat Cerebral Penetrating Arterioles
Authors: Dietrich Hans H. , Horiuchi Tetsuyoshi , Xiang Chuanxi , Hongo Kazuhiro , Falck J. Russell , Dacey, Jr. Ralph G.
Published: November 2008

Background: Adenosine triphosphate (ATP), a potent vascular regulator in the cerebral circulation, initiates conducted vasomotor responses which may be impaired after pathological insults. We analyzed the mechanism of ATP-induced local vasomotor responses and their effect on conducted vasomotor responses in rat cerebral penetrating arterioles. Methods: Arterioles were cannulated and their internal diameter monitored. Vasomotor responses to ATP were observed in the presence or absence of inhibitors, or after endothelial impairment. Smooth muscle membrane potentials were measured in some vessels. Results: Microapplication of ATP produced a biphasic response (constriction followed by dilation), which resulted in conducted dilation preceded by a membrane hyperpolarization. α,β-methylene-ATP or pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) blunted the ATP-mediated constriction and enhanced local and conducted dilation. Nω-monomethyl-L-arginine, endothelial impairment and N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH) reduced the local dilation caused by ATP. The conducted dilation was attenuated by MS-PPOH and endothelial impairment, but not Nω-monomethyl-L-arginine or indomethacin. Conclusion: ATP-induced conducted dilation is preceded by membrane hyperpolarization. Local ATP induces initial local constriction via smooth-muscle P2X1 and subsequent dilation via endothelial P2Y receptors. Nitric oxide, cytochrome P450 metabolites, and intermediate and large conductance KCa channels mediate dilation caused by ATP. ATP-induced conducted dilation is dependent upon both the endothelium and cytochrome P450 metabolites.
Activities of Daily Living, Cerebral Glucose Metabolism, and Cognitive Reserve in Lewy Body and Parkinson’s Disease
Authors: Perneczky Robert , Drzezga Alexander , Boecker Henning , Ceballos-Baumann Andres O. , Granert Oliver , Förstl Hans , Kurz Alexander , Häussermann Peter
Published: November 2008

Aims: (1) To investigate the neural substrate of impaired activities of daily living (ADL) in Lewy body-associated disorders, such as dementia with Lewy bodies, classical Parkinson’s disease, and Parkinson’s disease dementia, and (2) to explore the effect of education on the relationship between cerebral metabolic changes and ADL performance. Methods: Fifty-four patients with Lewy body-associated disorders underwent an extensive clinical evaluation including cerebral positron emission tomography with 18F-fluoro-2-deoxy-glucose scanning. First, those brain areas were identified where ADL performance and glucose metabolism were significantly correlated. Second, brain regions were detected where the association between metabolic changes and ADL performance differed significantly between patients with a low and a high educational background. Results: There was a significant association between glucose hypometabolism and impaired ADL performance in the prefrontal, temporoparietal, and occipital association cortices and the precuneus. However, there was a significantly stronger association between hypometabolism and impaired ADL in the low education group compared with the high education group in the right middle occipital gyrus. Conclusions: The study suggests (1) that brain metabolic alterations are significantly associated with the loss of everyday functioning in Lewy body-associated disorders and (2) that education modifies this association.
Fungal Peritonitis in Patients on Continuous Ambulatory Peritoneal Dialysis: A Single-Centre Experience in India
Authors: Ram R. , Swarnalatha G. , Neela P. , Dakshina Murty K.V.
Published: November 2008

Aims: The clinical features, treatment and outcome of fungal peritonitis (FP) in continuous ambulatory peritoneal dialysis (CAPD) patients were examined. Methods: Dialysis records of all 303 end-stage renal disease (ESRD) patients initiated on CAPD treatment between January 1998 and February 2008 were reviewed retrospectively. Results: In the 303 patients dialysed between January 1998 and February 2008, a total of 137 bacterial peritonitis and 43 FP episodes were recorded. The incidence rate of FP was 0.67/100 patient months or 1/148.67 months. It accounted for 23.88% of all peritonitis episodes. Three factors appeared to predict mortality: the presence of non-Candida species, the catheter being left in situ and a serum albumin level <3 g/dl. Multivariate analysis yielded only the latter 2 as predictors of mortality. The use of intraperitoneal antibiotics in the 3 months before infection and low serum albumin have been identified as risk factors for contracting FP. Conclusion: Risk factors for contracting FP and for mortality due to FP have been identified.
Renal Hemodynamics and Renoprotection
Authors: Loriga Giacomina , Vidili Gianpaolo , Ruggenenti Piero , Faedda Rossana , Sanna Marcella , Satta Andrea E.
Published: November 2008

Background: Angiotensin II (AII) is the well-known determinant of kidney damage increasing intraglomerular pressure, matrix expansion and fibroblast proliferation. Renin-angiotensin system (RAS) inhibition, limiting the hemodynamic effects of AII, reduces proteinuria and is renoprotective in the long term. Methods: We studied 15 chronic proteinuric patients by Doppler ultrasonography to clarify the intrarenal hemodynamic changes during RAS blockade by Benazepril (10–20 mg/day) alone and combined with Valsartan (80–160 mg/day). We also investigated the correlation between hemodynamic indices, RAS components and antiproteinuric effect. Results: After 1 month of Benazepril proteinuria, resistive index (RI) and pulsatility index (PI) significantly decreased and proteinuria reduction was directly correlated to decrease in RI (r = 0.55, p = 0.03). Contrarily, after 1 month of combined therapy, RI and PI restored to baseline and progressively increased in the following 3 months, while proteinuria decreased. Increase in RI was directly correlated to concomitant increase in plasma renin activity (r = 0.65, p = 0.01) suggesting a direct role of renin in restoring intrarenal resistances. Conclusion: The hemodynamic changes caused by RAS inhibitors partially contribute to the antiproteinuric effect. Other RAS components, such as renin, may contribute to renal vasoconstriction and could be a further determinant of kidney damage besides a promising target for renoprotection.
The Impact of Prior Multidisciplinary Predialysis Care on Mineral Metabolic Control among Chronic Hemodialysis Patients
Authors: Friedman Oded , Wald Ron , Goldstein Marc B.
Published: November 2008

Background/Aims: Disordered mineral metabolism is independently associated with mortality among chronic dialysis patients. We hypothesized that, upon dialysis start, biochemical markers of mineral metabolism would be better controlled among patients who had received multidisciplinary predialysis care (MDC). Methods: We conducted a retrospective cohort study of incident hemodialysis patients between 2002 and 2005. Corrected calcium (Ca), phosphate (P), calcium-phosphate product (Ca×P), and intact parathyroid hormone (iPTH) at the time of dialysis initiation and over the first year thereafter were compared based on prior MDC receipt. Furthermore, we examined the relationship between the duration of MDC and mineral metabolic parameters. Results: 67 patients received MDC and 84 patients received conventional or no nephrologist-based care. Patients who received MDC had a higher iPTH (p = 0.03) both at dialysis initiation and over the subsequent year while Ca, P, and Ca×P were not significantly impacted. Among patients who received MDC, mineral metabolic values at dialysis initiation did not differ by duration of predialysis care. Conclusions: The receipt of MDC had a limited effect on mineral metabolic profiles at the time of and over the first year following chronic hemodialysis initiation. The survival benefits associated with the receipt of MDC may be mediated by mechanisms other than improved mineral metabolic control.
Blood Monocyte Count Is a Predictor of Total and Cardiovascular Mortality in Hemodialysis Patients
Authors: Kato Akihiko , Takita Takako , Furuhashi Mitsuyoshi , Maruyama Yukitaka , Kumagai Hiromichi , Hishida Akira
Published: November 2008

An increase in white blood cell (WBC) count is an independent predictor of mortality in hemodialysis (HD) patients. However, few studies have assessed the association of specific WBC subtypes with mortality. We prospectively studied the predictive value of WBC subtypes for total and cardiovascular death in 333 HD patients (age 63 ± 12 years; HD duration 129 ± 109 months) during a 40-month of follow-up. There was a significant and positive correlation between highly sensitive C-reactive protein and neutrophil (r = 0.28, p < 0.01) and monocyte (r = 0.20, p < 0.01) counts by a non-parametric Spearman rank analysis. Blood monocyte counts were significantly correlated inversely with ankle-brachial pressure index (r = –0.24, p < 0.01). Kaplan-Meier analysis revealed that basal neutrophil (>4,060/μl) and monocyte (>270/μl) counts in the highest tertile had a significantly lower survival rate compared to the middle and the lowest tertiles, respectively (p < 0.03). Cox hazards analysis after adjustment for other conventional risk factors revealed that monocyte counts of >270/μl became a determinant of total death compared with those of <180/μl (hazards ratio 1.98 [1.10–3.57], p = 0.02). In contrast, neutrophil and lymphocyte counts were not associated with mortality. Our findings suggest that an increased blood monocyte count is an independent predictor of long-term mortality in chronic HD patients.
Catheter-Related Bacteremia in Hemodialysis: Which Preventive Measures to Take?
Authors: Silva Jorge , e Costa Teixeira , Baptista Alexandre , Ramos Aura , Ponce Pedro
Published: November 2008

Background: The use of tunneled hemodialysis catheters as definitive vascular access is becoming increasingly more widespread, reaching 25% of all dialysis patients in some countries. The rate of infectious morbidity and mortality is much higher when catheters are used than when patients are dialyzed through grafts or native fistulas, and it is generally agreed that implementing appropriate preventive measures would do more to lower its incidence. Methods: A prospective, randomized, open-label, long-term follow-up clinical trial was conducted to compare the efficacy of dressing the exit site with antibiotic ointment (AO) versus catheter antimicrobial locking (AL) in preventing catheter-related bacteremia (CRB), both associated with strict standard precautions and appropriate catheter care. A total of 141 tunneled catheters, newly implanted in 116 consecutive patients, were followed during a 2-year period. Patients were randomly distributed into one of three arms, with group A receiving AO prophylaxis, group B treated with a heparin + gentamicin (5.2 mg/ml) lock (AL) and group C receiving both AO and AL prophylaxis. Results: Group A had a significantly lower infection-free time survival curve (p < 0.02, Kaplan-Meier) with a catheter survival of 103.9 days and a significantly higher number of CRB (9 episodes, p < 0.02, χ2). Group B had 130.7 mean infection-free days and 1 episode of CRB. Group C had 127.3 mean infection-free days and 5 episodes of CRB. No toxicity or other adverse events were observed during this 2-year period, and the efficacy of the preventive measures remained stable throughout. Conclusion: Antimicrobial lock is superior to AO as a CRB preventive measure. The use of lock and ointment in the same catheter was not associated with additive effects.
Are Urinary Levels of Free Light Chains of Immunoglobulins Useful Markers for Differentiating between Systemic Lupus Erythematosus and Infection?
Authors: Mastroianni-Kirsztajn Gianna , Nishida Sonia K. , Pereira Aparecido B.
Published: November 2008

Introduction: Active systemic lupus erythematosus (SLE) and infection are often hard to distinguish. We evaluated the urinary levels of free light chains of immunoglobulins (urFLCIg) as a possible laboratory marker to differentiate those conditions. Methods: We evaluated 43 patients with lupus nephritis (16–63 years old), with or without concurrent infection (12 with infection), 14 with infectious disease without SLE and 20 with idiopathic Fanconi’s syndrome. The Systemic Lupus Erythematosus Disease Activity Index was utilized to establish activity of disease. Levels of urFLCIg kappa and lambda were determined by an immunoenzymometric assay developed in our institution. In order to evaluate proximal tubular dysfunction which could be responsible for increased levels of urFLCIg, we determined the low-molecular-weight protein urRBP. Results: Levels of urFLCIg in healthy volunteers (median kappa 1.57 mg/l; lambda 0.96 mg/l), inactive SLE (5.36; 4.93) and active SLE (11.82; 23.59) were significantly different; urFLCIg levels or urFLCIg/urRBP ratios could not separate patients with infection from those with SLE. Conclusion: Our data show that convoluted proximal tubular dysfunction was not responsible for the increase in urFLCIg levels. UrFLCIg determination was useful in the detection of SLE activity, but was unable to distinguish activity from infection in this condition.
The Effect of Volume of Chorionic Villi on Long-Term Cell Culture
Authors: Chen Min , Ng Lucy , Lau Elizabeth , Lee Chin Peng , Tang Mary Hoi Yin , Lam Yung Hang
Published: November 2008

Objective: It was the aim of our study to investigate the association between culture time and weight of villi obtained by transabdominal chorionic villus sampling (CVS). Methods: We analyzed 1,442 villus samples. Results: The gestational age at sampling ranged from 10 to 14 weeks. The weight of villi in these samples ranged from 1 to 80 mg (median 10 mg, interquatile range 7–12 mg). The culture time ranged from 5 to 24 days. Culture time was significantly and inversely correlated with the weight of villi obtained (r = –0.258, p < 0.01). Time was significantly longer when 5 mg or less of villi was obtained but the difference was only up to 2 days. Conclusions: Because the difference in culture time for different groups of villus samples was within 1–2 days, this relationship is statistically significant but has no clinical significance.
Mycophenolate Mofetil Treatment for IgA Nephropathy: A Meta-Analysis
Authors: Xu Gaosi , Tu Weiping , Jiang Dongfeng , Xu Chengyun
Published: November 2008

Background: Worldwide, IgA nephropathy (IgAN) is the most common type of glomerulonephritis. Mycophenolate mofetil (MMF) is relatively selective for lymphocytes and inhibits antibody production by B cells more than other immunosuppressants. Several randomized controlled trials (RCTs) have analyzed the role of MMF in patients with IgAN. We conducted this meta-analysis of all available RCTs to ascertain the benefits and risks of MMF treatment in comparison with placebos or steroids in patients with IgAN. Methods: The studies were identified by extended computer- based searches of the PubMed database (April, 2008) and the Cochrane Library, without language restriction. References in Medline-cited studies were reviewed to identify additional reports not indexed by Medline. RCTs comparing treatment of IgAN with mycophenolate against placebo or steroids were included in the analysis. Results: We identified 32 potentially relevant articles, but only 4 RCTs, which had enrolled a total of 168 patients, were included. Our meta-analysis demonstrated that MMF treatment did not have statistically significant effects in reducing proteinuria or protecting renal function in patients with IgAN. Conclusion: The currently available evidence does not support the routine use of MMF in patients with IgAN. Larger international collaborations should be put in place to further address this issue.
Serum Uric Acid and Endothelial Dysfunction in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: Tang Ziyong , Cheng Li-Tao , Li Hong-Yan , Wang Tao
Published: November 2008

Background: Endothelial dysfunction is an early predictor of cardiovascular events. Hyperuricemia has been shown to be associated with increased cardiovascular mortality. It remains unclear if serum uric acid (UA) is associated with endothelial dysfunction in peritoneal dialysis patients. Methods: In this cross-sectional study, the relationship of UA and endothelial dysfunction was investigated in 189 stable peritoneal dialysis patients. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. Results: UA levels did not differ between 93 male and 96 female patients (416.31 ± 86.93 vs. 395.52 ± 87.47 μmol/l, p > 0.05). Patients were grouped into three tertiles on the basis of their serum UA levels. Systolic blood pressure (p = 0.007), serum phosphate (p = 0.005), high-sensitive C-reactive protein (hs-CRP) (p < 0.001), and FMD (p = 0.016) were all different among UA tertiles. FMD was found to be related with UA (p = 0.002) and hs-CRP (p = 0.006) in a Pearson’s correlation analysis. Multivariate regression analysis showed that only UA was an independent determinant of FMD (β = –0.237, p = 0.036). Conclusion: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.
Comparison of Ankle-Brachial Index and Brachial-Ankle Pulse Wave Velocity between Patients with Chronic Kidney Disease and Hemodialysis
Authors: Chen Szu-Chia , Chang Jer-Ming , Hwang Shang-Jyh , Chen Jui-Hsin , Lin Feng-Hsien , Su Ho-Ming , Chen Hung-Chun
Published: November 2008

Background/Aims: Patients with chronic renal failure are highly predisposed to atherosclerosis. However, there is limited data about the direct comparison of atherosclerosis between patients with chronic kidney disease (CKD) and hemodialysis. The aim of this study was to compare ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) between patients with CKD and hemodialysis and thus examined the status of peripheral artery occlusive disease (PAOD) and arterial stiffness between them. Methods: We enrolled 169 patients with CKD stage 3–5 and 225 hemodialysis patients in one regional hospital. ABI and baPWV were measured by using an ABI-form device (VP1000, Colin). Results: A higher prevalence of ABI <0.9 was found in hemodialysis patients than in CKD patients (15.6 vs. 8.3%, p = 0.030). After a multivariate analysis, ABI <0.9 was associated with increased age, diabetes mellitus (DM), increased pulse pressure, decreased serum albumin level, and hemodialysis treatment. The baPWV was positively associated with age, DM, systolic and diastolic blood pressures, and negatively with body mass index. However, after adjusting for other variables, baPWV was comparable between patients with CKD and hemodialysis. Conclusions: The study revealed that PAOD might be more prevalent in patients with hemodialysis than in patients with CKD, but arterial stiffness might be comparable between them.