bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Day Enteral Exposure to a Red Kidney Bean Lectin Preparation Enhances the Pancreatic Response to CCK Stimulation in Suckling Pigs
Authors: Evilevitch L. , Pierzynowski S.G. , Linderoth A. , Ahrén B. , Erlanson-Albertsson Ch. , Podgurniak M. , Weström B.R.
Published: September 2004

Background: A reason for the digestive problems that often occur around early weaning in piglets could be that the pancreas is not yet fully developed and the enzymes required for degradation of the solid food are not secreted in enough amounts. Objectives: The aim of the study was to investigate the possibility of inducing pancreas maturation with enhanced enzyme secretion. Methods: 10-day-old suckling pigs were gavage fed with a red kidney bean lectin preparation for 3 days, and the pancreatic response to intravenous infusion of CCK-33 was measured in the anaesthetized animals fitted with pancreatic duct catheters. Results: The pancreatic fluid secretion, protein output, and the trypsin and amylase outputs were significantly increased in response to CCK stimulation after the lectin treatment, as compared to those of the control littermates (p ≤ 0.05). In addition, the plasma insulin basal levels and those observed during CCK-33 stimulation were lower in the lectin-treated piglets. Conclusion: The results suggested that the lectin treatment led to an increase in the capacity for pancreatic enzyme secretion in the suckling piglets. An enhanced pancreatic function might help to ameliorate the problems that may appear in modern pig production which are associated with weaning.
Itch: More than Skin Deep
Authors: Greaves Malcolm W. , Khalifa Nedha
Published: September 2004

Recent research in neurophysiology of itch has indicated the existence of itch-dedicated nociceptor neurones. The perception of itch is regulated by tonically inhibitory descending neuronal pathways and nociceptor spinal neuronal circuits. There is at present no convincing evidence of an ‘itch centre’ in the brain. A classification of itch has been proposed, based on neurophysiological considerations, which stresses the importance of neurogenic and neuropathic itch, and assists in differential diagnosis and selection of treatment. However, more than one class of itch can occur concurrently in the same patient. The importance of cross- talk between dermal mast cells and nociceptor nerve terminals, involving cleavage of proteinase-activated receptor 2 by mast cell tryptase, is highlighted. The pruritus of cholestasis is mediated at least in part by opioid peptides synthesized by the liver, and elevated levels of these mediators are found in the plasma and skin of patients with itch due to cholestasis. The combined use of both µ- receptor antagonists and ĸ-receptor agonists (anti-pruritic) is worth exploring.
Insights into the Pathogenesis of Asthma Utilizing Murine Models
Authors: Taube Christian , Dakhama Azzeddine , Gelfand Erwin W.
Published: September 2004

Asthma is a common syndrome in children and adults. Despite the increasing prevalence and socioeconomic burden, the underlying pathophysiology remains poorly defined in a large percentage of asthmatics. Animal models and, in particular, murine models of allergic airway disease have helped to reveal some of the potential underlying mechanisms and have played an important role in identifying the importance of T cells and TH2 cytokines in development of allergen-induced inflammation and airway hyperresponsiveness. In addition, other cell types including mast cells and eosinophils have been implicated in the development of some aspects of the disease. To further understand this complex syndrome, the development of animal models which mimic elements of this chronic airway disease is essential.
Effects of Ursodeoxycholic Acid on Synthesis of Cholesterol and Bile Acids in Healthy Subjects
Authors: Sauter Gerd H. , Thiessen Kai , Parhofer Klaus G. , Jüngst Christoph , Fischer Sven , Jüngst Dieter
Published: September 2004

Background/Aims: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7α-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24–44 years) in a single dose of 10–15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7α-hydroxy-4-cholesten-3-one (7α-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman’s rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7α-HCO serum concentrations from 39.7 ± 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 ± 30.4 ng/ml (median 77.5 ng/ml) at days 30–40 of UDCA treatment (p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.
Accumulation of 8-Hydroxy-2’- Deoxyguanosine Adducts in HBx Recombinant HepG2 Cells and HBx Transgenic Mice
Authors: Gehrke Ralph , Brauchle Maria A. , Reifenberg Kurt , Hildt Eberhard , Gruetzner Uwe , Schmitz Volker , Schlicht Hans-Jürgen , Hofschneider Peter Hans , Caselmann Wolfgang H. , Rabe Christian
Published: September 2004

Background/Aims: Transgenic mice overexpressing hepatitis B x protein (HBx) show an increased susceptibility to mutations if exposed to mutagens. Also involved in HBx signalling, reactive oxygen intermediates (ROI) can induce DNA adducts such as 8-hydroxy-2′-deoxyguanosine that can in turn lead to G/T transversion mutations. Therefore, we investigated whether HBx expression increases the level of the mutational precursor 8-hydroxy-2′-deoxyguanosine in hepatocellular DNA. Methods: 8-hydroxy-2′-deoxyguanosine concentrations of DNA hydrolysates of HBx protein expressing HepG2 cells and livers of HBx transgenic mouse lines were determined electrochemically after HPLC fractionation. Results: 8-hydroxy-2′-deoxyguanosine concentrations in genomic DNA of HBx protein expressing cell lines correlated with the factor of transactivation. The 8-hydroxy-2′-deoxyguanosine levels were reduced after incubation of HBx recombinant cell lines with 0.1 or 1 mM of the antioxidant N-acetylcysteine. Hepatic 8-hydroxy-2′-deoxyguanosine concentrations in DNA of old transgenic mice were significantly, i.e. twofold, (p < 0.01) increased as compared to those of old nontransgenic or young transgenic controls and of control mice expressing a second HBV transactivator (MHBst76). Conclusion: HBx expression results in elevated DNA adduct levels. This could reflect a direct inhibitory interaction of HBx with cellular repair mechanisms. Alternatively, this may be an effect of an increased generation of reactive oxygen intermediates through HBx.
Spatial and Temporal Pattern of Expression of Interstitial Collagenase, Stromelysin/Transin, Gelatinase A, and TIMP-1 during Experimental Gastric Ulcer Healing
Authors: Calabrò Antonio , Grappone Cecilia , Pellegrini Giulia , Evangelista Stefano , Tramontana Manuela , Schuppan Detlef , Herbst Hermann , Milani Stefano
Published: September 2004

Background/Aim: Controlled proteolysis is a prerequisite for cell migration, angiogenesis, and matrix remodelling during gastric ulcer healing. We studied the temporal and spatial expression of three matrix metalloproteinases, gelatinase A (MMP-2), interstitial collagenase (MMP-13), stromelysin (MMP-3), and their major inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1) during experimental gastric ulcer healing induced in rats by acetic acid injection. Methods: Gastric tissue specimens were hybridized with antisense 35S-labelled RNA probes and the autoradiographic signal was analyzed by a computer aided image system. Gelatinase activity was analyzed by in situ and gel zymography. Results: During gastric ulcer healing, MMP-2, MMP-3, and MMP-13 RNA expression was increased in stromal cells of the gastric mucosa bordering the ulcer, suggesting a prevalent role of non-epithelial cells in pericellular proteolysis. Gelatinolytic activity was increased during ulcer healing and it was associated with extracellular matrix of the healing mucosa and newly formed vessels. In contrast to MMP-2 RNA, which was homogeneously distributed in all layers of the ulcer bed, MMP-3 and MMP-13 RNAs were confined to the upper layers of the granulation tissue. TIMP-1 RNA was detected in both epithelial and stromal cells of the gastric mucosa adjacent to the ulcer, as well as in the granulation tissue of the ulcer bed. Both MMP and TIMP-1 expression returned to basal levels during the late stages of tissue remodeling. Conclusion: Gastric ulcer repair is associated with a transient expression of specific metalloproteinases and their inhibitors in a distinct anatomical pattern pointing to complex cellular and cell/matrix interactions in the various layers of the healing mucosa.
Cystatin C as a Marker of Residual Renal Function during Continuous Hemodiafiltration
Authors: Balík Martin , Jabor Antonín , Waldauf Petr , Kolář Michal , Pavlisová Marie , Břešt’an Daniel , Hendl Jan , Rychlík Ivan
Published: September 2004

Background: The level of residual renal function (RRF) has an important impact on follow-up in critically ill patients with renal failure. There is currently no clear marker of RRF. Methods: Cystatin C (cysC) concentrations were measured before and during the first 48 h of CVVHDF in 33 mechanically ventilated patients suffering from renal failure. Samples were drawn both from the ports proximal and distal to the filter. Each of the two control groups consisted of 10 patients. Results: The levels of cysC were significantly higher in the group where diuresis (Vu) remained low or decreased after 48 h of treatment (n = 21, Vu median 380 (80–935) ml/24 h, cysC range 4.44–3.42 mg/l) than in the group where Vu increased to the level of 1.5 ml·kg–1·h–1 or higher after 48 h of treatment (n = 12, Vu 4,570 (4,000–5,130) ml/24 h, cysC 3.17–2.46 mg/l, p < 0.01). Creatinine clearance taken before treatment was not different between the groups. Significant correlation between cysC levels and Vu was found (r = –0.44, p < 0.0001). CysC levels were significantly higher in non-survivors than in survivors (3.54 ± 1.38 vs. 3.07 ± 1.24, p < 0.03). Conclusion: The levels of cysC are inversely related to Vu. High levels of cysC are associated with low residual diuresis, longer duration of CVVHDF and higher intensive care unit mortality in patients treated with CVVHDF.
Resuscitation of Depressed Newborn Infants with Ambient Air or Pure Oxygen: A Meta-Analysis
Authors: Saugstad Ola Didrik , Ramji Siddarth , Vento Máximo
Published: September 2004

Background: It is discussed whether depressed newborn infants should be resuscitated with room air or 100% O2. Objective: To perform a systematic review and meta-analysis including studies that report resuscitation of depressed newly born infants with 21 or 100% O2. Methods: Inclusion criterion was randomized or pseudo-randomized, blinded or not, studies of depressed newborn infants resuscitated with either 21 or 100% O2. The literature was searched in Medline/Pubmed/EMBASE and The Cochrane library databases. All identified studies were included. Results: Five studies fulfilled the inclusion criterion in which 881 infants were resuscitated with 21% O2 and 856 with 100% O2. Neonatal mortality was 8.0 vs. 13.0% in the 21 and 100% O2 groups respectively, OR 0.57, 95% CI 0.42–0.78. In term infants neonatal mortality was 5.9% in the 21% O2 group and 9.8% in the 100% O2 group, OR 0.59, 95% CI 0.40–0.87. The figures for the premature infants were very similar. In infants with 1-min Apgar score <4, OR for neonatal mortality was 0.81 (95% CI 0.54–1.21). Apgar score at 5 min and heart rate at 90 s were significantly higher, and time to first breath significantly earlier in infants given 21% O2 compared with 100% O2. Conclusions: A systematic review and meta-analysis demonstrated that neonatal mortality is significantly reduced when depressed newly born infants are resuscitated with ambient air instead of pure oxygen. For infants with low 1-min Apgar score (<4), no significant difference in neonatal mortality was found. Recovery was faster in infants resuscitated with 21% O2 than 100% O2.
Decreased Release of the Angiogenic Peptide Vascular Endothelial Growth Factor in Alzheimer’s Disease: Recovering Effect with Insulin and DHEA Sulfate
Authors: Solerte Sebastiano Bruno , Ferrari Ettore , Cuzzoni Gianni , Locatelli Eleonora , Giustina Andrea , Zamboni Mauro , Schifino Nicola , Rondanelli Mariangela , Gazzaruso Carmine , Fioravanti Marisa
Published: September 2004

Changes of vascular endothelial growth factor (VEGF) secretion have recently been demonstrated in patients with Alzheimer’s disease (AD). Since VEGF has been involved in brain angiogenesis, neuroprotection and cerebromicrovascular exchange of substrates and nutrients, the study of VEGF could have important relapses into the pathogenesis and treatment of AD. Within this context, 35 healthy subjects (16 of young and 19 of old age), 18 patients with dementia of the vascular type (VAD) and 22 with dementia of the Alzheimer’s type (AD) were included in the study. VEGF levels were determined in the supernates of circulating natural killer (NK) immune cells isolated by immunomagnetic separation (pure CD16 + CD56 + NK cells at a final density of 7.75 × 106 cells/ml). VEGF was measured in spontaneous conditions (without modulation) and after exposure of NK cells with IL-2, lipopolysaccharide (LPS), dehydroepiandrosterone sulfate (DHEAS), LPS + insulin, amyloid-β (Aβ) fragment 1–42, the inactive sequence Aβ40–1 and Aβ1–42 + insulin. A significant decrease in VEGF released by NK cells was demonstrated in AD subjects compared to the other groups. No differences of VEGF levels were found between healthy subjects of old age and the VAD group. The incubation with LPS and DHEAS significantly increased, in a dose-dependent manner, VEGF levels in AD as well as in healthy subjects of young and old age and in VAD patients. The incubation of NK cells with Aβ1–42 completely suppressed VEGF generation in AD subjects, also reducing VEGF release in the other groups. The co-incubation of NK with LPS + insulin, at different molar concentrations, significantly restored (4- and 6-fold increase from LPS alone) VEGF in AD, also enhancing VEGF secretion in healthy subjects and the VAD group, while the co-incubation of NK with Aβ1–42 + insulin promptly abolished the negative effects of Aβ1–42 on VEGF release. These data might suggest that the decreased VEGF secretion by peripheral immune cells of AD subjects could have a negative role for brain angiogenesis, neuroprotection and for brain microvascular permeability to nutrients, increasing brain frailty towards hypoxic injuries. On the contrary, insulin and DHEAS could have beneficial effects in AD, as well as in VAD and in physiological aging, by increasing, in a dose-dependent fashion, VEGF availability by peripheral and resident immune and endothelial cells, so contributing to increase its circulating pool.
Current Smoking and Response to Cholinesterase Inhibitor Therapy in Alzheimer’s Disease
Authors: Connelly Peter J. , Prentice Neil P.
Published: September 2004

Current smoking has been suggested as predicting poor response to cholinesterase inhibitor treatment. This observational study compares response in subjects with NINCDS-ADRDA ‘probable’ Alzheimer’s disease who are current smokers and subjects who are non-smokers. Smoking status was not associated with response. Smokers were significantly more likely to improve Digit Symbol Substitution Test (DSST) scores following treatment. In non-smokers, improvement from baseline DSST scores was associated with good response but this was not the case in smokers. The change in the DSST is in keeping with smokers having increased numbers of nicotinic receptors. In smokers, the lack of association between improvement in DSST scores and good response may be representative of inhibitory properties of cigarette smoke that are unrelated to nicotine.
The French Addenbrooke’s Cognitive Examination Is Effective in Detecting Dementia in a French-Speaking Population
Authors: Bier J.-C. , Donckels V. , van Eyll E. , Claes T. , Slama H. , Fery P. , Vokaer M.
Published: September 2004

We evaluated the sensitivity and specificity of our French version of Addenbrooke’s cognitive examination (ACE) to detect dementia in our patient population. One hundred and fifty-eight cases were included in the study. In our patient series, the sensitivity for diagnosing dementia with a Mini-Mental State Examination (MMSE) score of ≤24/30 was 48.5%, the sensitivity of an MMSE score of ≤27/30 was 82.5% with a specificity of 72.1%, the sensitivity of an ACE score of ≤83/100 was 86.6% with a specificity of 70.5% and the sensitivity of an ACE score of ≤88/100 was 97.9% with a specificity of 59%. We conclude that the French version of the ACE is a very accurate test for the detection of dementia, and should be widely used in clinical practice.
[18F]FDG-PET in Patients with Alzheimer’s Disease: Marker of Disease Spread
Authors: Bittner D. , Grön G. , Schirrmeister H. , Reske S.N. , Riepe M.W.
Published: September 2004

Background: It is not known yet whether temporoparietal glucose hypometabolism in patients with probable Alzheimer’s disease (AD) reflects disease severity or different subtypes of patients. Methods: Twenty-five subjects with mild probable AD [NINCDS-ADRDA criteria; age 65.8 ± 9.3 years (mean ± SD); Mini-Mental State Examination (MMSE) 26.0 ± 3.3] were investigated. [18F]FDG-PET data were analyzed visually with raters blinded to the diagnosis and with a quantitative analysis in the region of interest on individual anatomically normalized PET scans. Results: Thirteen of 25 patients showed temporoparietal hypometabolism on visual inspection (PET+; age 65.7 ± 10.7), 12 patients had normal FDG-PET results (PET–; age 65.9 ± 8.0; n.s.). The MMSE and immediate reproduction of the Wechsler Memory Scale (WMS-R-I) were 27.7 ± 1.9 and 31.1 ± 6.1 in the PET– vs. 24.5 ± 3.6 (p = 0.012) and 22.0 ± 7.4 (p = 0.006) in the PET+ group. Immediate and delayed recall in the California Verbal Learning Test and delayed reproduction in the Wechsler Memory Scale were alike. Regression analysis revealed a significant correlation of temporoparietal glucose metabolism with the block span (r = 0.60; p < 0.01) and the WMS-R-I (r = 0.68; p < 0.01) but not with measures of hippocampal function. Conclusions: Temporoparietal glucose metabolism in patients with very mild AD is a sign of disease spread beyond the temporal lobe. This may aid in establishing objective parameters for future therapeutic studies.
Association Analysis for the Muscarinic M1 Receptor Genetic Polymorphisms and Alzheimer’s Disease
Authors: Liu Hsiu-Chih , Hong Chen-Jee , Liu Tsung-Yun , Chi Chin-Wen , Tsai Shih-Jen
Published: September 2004

In the ongoing search to reveal the pathophysiology of Alzheimer’s disease (AD), the cholinergic system is important due to its role in cognitive function and its significance with respect to the results of postmortem pathology and animal model studies. For this investigation, we tested the hypothesis that the allelic variant (C267A) of the cholinergic receptor muscarinic 1 (CHRM1) confers susceptibility to AD or is related to its age of onset, in a sample population of 232 AD patients and 169 normal controls. The distribution of the CHRM1 genotypes (p = 0.919) and alleles (p = 0.327) did not differ significantly comparing AD patients and controls, even after stratification according to apolipoprotein E genotype. The onset age was not significantly different comparing the CHRM1 genotype groups. Our negative findings suggest that it is unlikely that the CHRM1 C267A polymorphism plays a substantial role in conferring susceptibility to AD. We propose that other genetic variations of CHRM1, relating either to AD or to the therapeutic response for AD, may need further investigation.
A 12-Month Study of the Efficacy of Rivastigmine in Patients with Advanced Moderate Alzheimer’s Disease
Authors: Karaman Yahya , Erdoğan Füsun , Köseoğlu Emel , Turan Tayfun , Ersoy Ali Özdemir
Published: September 2004

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer’s disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 ± 1.0, 8.3 ± 1.2, 8.9 ± 1.3, and 10.7 ± 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6–12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.
Brain Natriuretic Peptide Levels Fall Rapidly after Cardioversion of Atrial Fibrillation to Sinus Rhythm
Authors: Vinch Craig S. , Rashkin Jason , Logsetty Giridhar , Tighe Dennis A. , Hill Jeffrey C. , Meyer Theo E. , Rosenthal Lawrence S. , Aurigemma Gerard P.
Published: September 2004

Background: Brain natriuretic peptide (BNP) levels have been reported to fall following cardioversion of atrial fibrillation (AF). The mechanism for the fall in BNP has not been elucidated and the potential confounding effects of sedation have not been investigated. Sedation may alter BNP levels via its effects on loading conditions. Accordingly, we studied whether BNP levels change shortly after cardioversion and attempted to control for possible effects of sedation. Methods: BNP levels were obtained before and after cardioversion in patients with AF and in a control group of patients undergoing intravenous conscious sedation for transesophageal echocardiography. Results: BNP levels dropped (260 ± 255 vs. 190 ± 212 pg/ml, p < 0.05) 40 min after cardioversion, decreasing in 33 of 41 subjects who achieved sinus rhythm. By contrast, mean BNP did not fall in subjects in whom cardioversion was not successful. The change in BNP level was not related to the degree of change in heart rate. No control subject experienced a change in cardiac rhythm; BNP levels increased (195 ± 407 vs. 238 ± 458 pg/ml, p < 0.05) in 18/22 subjects after sedation. Baseline BNP levels were elevated in subjects with AF, and BNP levels were elevated in parallel with heart failure symptoms. Conclusions: The rapid fall in BNP after cardioversion (1) may reflect prompt hemodynamic improvement associated with rhythm change and (2) does not appear to be due to the effects of sedation.
Color Doppler Tissue Velocity Imaging Demonstrates Significant Asynchronous Regional Left Ventricular Contraction and Relaxation in Patients with Bundle Branch Block and Heart Failure Compared with Control Subjects
Authors: Schuster Peter , Faerestrand Svein , Ohm Ole-Jørgen
Published: September 2004

Bundle branch block in patients with severe heart failure (HF) may result in asynchronous regional left ventricular (LV) contraction. Colour Doppler tissue velocity imaging (c-TVI) allows tissue velocity profiles to be measured with a resolution of 10 ms. Normal subjects (n = 30) showed a synchronous regional longitudinal LV pattern of movement, and HF patients with bundle branch block (n = 30) showed asynchronous contraction and relaxation patterns which were quantified by c-TVI as ranging from –22 to 19 ms. This asynchronous LV contraction probably contributes to the deterioration of LV function in HF patients.
Vitamin D Insufficiency and Deficiency in Chronic Kidney Disease
Authors: González Esther A. , Sachdeva Ashutosh , Oliver Dana A. , Martin Kevin J.
Published: September 2004

Background: Kidney disease has been identified as a risk factor for vitamin D deficiency in hospitalized patients, and low levels of 25-hydroxyvitamin D have been suggested to be a risk factor for hyperparathyroidism in patients with chronic kidney disease (CKD). However, little is known about the magnitude of vitamin D deficiency in patients with CKD living in the United States. Methods: In this regard, we examined the levels of 25(OH)D in 43 patients with CKD and serum creatinine between 1 and 5 mg/dl (calculated glomerular filtration rate 111–11 ml/min per 1.73 m2) as well as in 103 patients undergoing hemodialysis. Results: In the predialysis patients, we found that 37 of the 43 patients (86%) had suboptimal levels of vitamin D (<30 ng/ml). Regression analysis indicated that there was a negative correlation between 25(OH)D and intact parathyroid hormone (PTH). Alkaline phosphatase showed a similar but less sensitive relationship. Serum albumin levels correlated with 25(OH)D levels. In contrast to findings reported in normal individuals, the levels of calcitriol correlated with those of 25(OH)D in the patients with CKD. In the group undergoing maintenance hemodialyis, we found that 97% of the patients had vitamin D levels in the suboptimal range, and there was no correlation of 25(OH)D levels with either PTH or serum albumin values. These data indicate that vitamin D insufficiency and deficiency are highly prevalent in patients with CKD and may play a role in the development of hyperparathyroidism. The functional significance of low levels of 25(OH)D in patients with stage 5 CKD remains to be determined.
Activity of Nadifloxacin (OPC-7251) and Seven Other Antimicrobial Agents against Aerobic and Anaerobic Gram-Positive Bacteria Isolated from Bacterial Skin Infections
Authors: Nenoff P. , Haustein U.-F. , Hittel N.
Published: September 2004

Background and Methods: The in vitro activity of nadifloxacin (OPC-7251), a novel topical fluoroquinolone, was assessed and compared with those of ofloxacin, oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and 2 Propionibacterium granulosum strains. All strains originated from bacterial-infected skin disease and were isolated from patients with impetigo, secondary infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis. In vitro susceptibility of all clinical isolates was tested by agar dilution procedure and minimum inhibitory concentrations (MICs) were determined. Results: Nadifloxacin was active against all aerobic and anaerobic isolates. MIC90 (MIC at which 90% of the isolates are inhibited) was 0.1 µg/ml for S. aureus, 0.78 µg/ml for both Streptococcus spp. and CNS, and 0.39 µg/ml for Propionibacterium spp. On the other hand, resistant strains with MICs exceeding 12.5 µg/ml were found in tests with the other antibiotics. For both CNS and Propionibacterium acnes, MIC90 values ≧100 µg/ml were demonstrated for erythromycin. Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin exhibited MIC90 values ≤1 µg/ml for some bacterial species tested. Both oxacillin and flucloxacillin were active against all investigated bacterial species with MIC90 values ≤1 µg/ml. Conclusion: In summary, nadifloxacin, a topical fluoroquinolone, was found to be highly active against aerobic and anaerobic bacteria isolated from patients with infected skin disease, and seems to be a new alternative for topical antibiotic treatment in bacterial skin infections.
Dialyzing a Patient with Human Immunodeficiency Virus Infection: What a Nephrologist Needs to Know
Authors: Mandayam Sreedhar , Ahuja Tejinder S.
Published: September 2004

The percentage of dialysis centers that have reported dialyzing human immunodeficiency virus (HIV)-infected patients increased from 11% in 1985 to 37% in 2000. Being primary care physicians for the dialysis patients, nephrologists are frequently confronted with the management of HIV-infected dialysis patients especially in urban centers. The aims of the present review are to discuss issues that are unique to HIV infection and end-stage renal disease, and to provide dialysis caretakers with sufficient information to help them optimize care and improve outcomes of these patients. Issues related to the choice of renal replacement therapy, vascular access, management of anemia, vaccination, and antiretroviral therapies are discussed in detail.
Creutzfeldt-Jakob Disease and Cadaveric Dura Mater Grafts in Japan: An Updated Analysis of Incubation Time
Authors: Matsui Shigeyuki , Sadaike Tetsuji , Hamada Chikuma , Fukushima Masanori
Published: September 2004

The incubation time for 76 patients with cadaveric dura mater-transmitted Creutzfeldt-Jakob disease reported in Japan by November 2001 was analyzed to clarify its distributional feature and the risk factors which affect the earlier onset of the disease. Cluster analysis indicated that cases could be divided into 3 clusters with respect to the incubation time, i.e., short (1.4–6.2 years), medium (7.0–11.9 years) and long (12.9–17.6 years). The incubation time in females was significantly shorter than those in males. Patients who were transplanted dura mater for facial spasms had a significantly shorter incubation time than those who received transplantation for other diseases including meningioma, aneurysm, or acoustic schwannoma. These results suggest that some host factors may have an influence on the incubation time of the disease.
Seasonal Patterns of Incidence and Case Fatality of Stroke in Malmö, Sweden: The STROMA Study
Authors: Khan Farhad Ali , Engstrom Gunnar , Jerntorp Ingela , Pessah-Rasmussen Hélène , Janzon Lars
Published: September 2004

Background: Studies on the temporal variation in stroke incidence have reported inconsistent results. Few have studied the temporal variations in case fatality. No study on incidence and case fatality of stroke by season in Sweden has been found. This study explores the weekly, monthly and seasonal variations in incidence and 28-day case fatality of stroke. Methods: A total of 7,129 patients with first-ever stroke during the period 1989–1999 were retrieved from the Stroke Register of Malmö, Sweden. χ2 test was performed to test the seasonal differences and Poisson regression analysis was used to calculate the case fatality ratios adjusted for sex and age. Results: The stroke cases were on the whole randomly distributed over the study period of 4,017 days. Incidence of all types of stroke, intracerebral hemorrhage and subarachnoid hemorrhage showed no variation by season, month or weekday, but incidence of cerebral infarction for the total population was higher in autumn and winter. Twenty-eight-day case fatality (930 fatal events, 13%) clustered significantly over the study period. Winter emerged as the peak season among men (12.5%), women (17.2%) and total population (15.1%). No consistent variation of incidence and case fatality of stroke by month or weekday was found. Conclusion: Case fatality after stroke demonstrates a seasonal variation with a peak in winter. Incidence of stroke showed no consistent association with season, month or weekday.
No Major Birth Order Effect on the Risk of Multiple Sclerosis
Authors: Ahlgren Cecilia , Andersen Oluf
Published: September 2004

In the present study, we found no association between multiple sclerosis (MS; definite and probable, n = 211) and birth order (p = 0.1411). The observed number of first-born patients did not differ significantly from the expected number (p = 0.0871). While there was a significantly high birth order (n = 258, p = 0.0381) and a marginally significant low number of first-borns (p = 0.0475) when possible MS cases were included, an artefact due to the population structure may have accentuated this result. In comparison with the control birth cohort, there was no significant association with birth order (p = 0.0742) or the proportion of first-borns (p = 0.220) in a subgroup from the MS incidence cohort born between 1915 and 1929 (n = 158). Birth order had no major impact on the risk of subsequent MS in this study.
Cardiovascular Risk Factors and Cognitive Function in Adults 30–59 Years of Age (NHANES III)
Authors: Pavlik Valory N. , Hyman David J. , Doody Rachelle
Published: September 2004

In the Third National Health and Nutrition Examination Survey (NHANES III), three measures of cognitive function [Simple Reaction Time Test (SRTT), Symbol Digit Substitution Test (SDST), and Serial Digit Learning Test (SDLT)] were administered to a half-sample of 3,385 adult men and nonpregnant women 30–59 years of age with no history of stroke. We used multiple linear regression analysis to determine whether there was an independent association between performance on each cognitive function measure and defined hypertension (HTN) alone, type 2 diabetes mellitus (DM) alone, and coexistent HTN and DM after adjustment for demographic and socioeconomic variables and selected health behaviors. After adjustment for the sociodemographic variables, the combination of HTN + DM, but not HTN alone or DM alone, was significantly associated with worse performance on the SRTT (p = 0.031) and the SDST (p = 0.011). A similar pattern was observed for SDLT performance, but the relationship did not reach statistical significance (p = 0.101). We conclude that HTN in combination with DM is associated with detectable cognitive decrements in persons under age 60.
Comparison of Stroke Risk Factors and Outcomes in Patients with English-Speaking Background versus Non-English-Speaking Background
Authors: Shen Qing , Cordato Dennis J. , Chan Daniel K.Y. , Kokkinos James
Published: September 2004

This study examined stroke risk factor profiles, management and outcomes for elderly patients with English-speaking background (ESB) and non-English-speaking background (NESB). This is an observational cohort study with both retrospective and prospective components. In total, 186 consecutive acute stroke patients aged ≧65 years admitted to our hospital were recruited over a 12-month period. Patient characteristics, stroke risk factors and management, in-hospital mortality, functional independence measurement scores before admission and at discharge, and discharge destination were recorded. On admission, NESB patients with atrial fibrillation (AF) were less likely to be taking warfarin than ESB patients (1 out of 19 with NESB vs. 19 out of 41 with ESB, p = 0.001). More NESB patients had a history of diabetes mellitus (DM) than ESB patients (41.4 vs. 10.2%, respectively; p = 0.001). However, ESB and NESB patients were comparable in terms of age, gender, preadmission functional status as well as other stroke risk factors (including smoking and alcohol drinking pattern, prevalence of hypertension and lipid disorder) and their management. In-hospital mortality was similar between ESB and NESB patients (10.2 vs. 8.6%). In conclusion, we found an association with our population of elderly NESB patients and an underutilization of warfarin for AF as well as a higher frequency of DM. Determination of the underlying reasons for such differences may be of value in the primary health care of NESB patients.
Frequency and Risk Factors of Vascular Cognitive Impairment Three Months after Ischemic Stroke in China: The Chongqing Stroke Study
Authors: Zhou David H.D. , Wang John Y.J. , Li Jingcheng , Deng Juan , Gao Changyue , Chen Man’e
Published: September 2004

Background: Frequency of poststroke cognitive impairment is high in western countries, and the risk factors of poststroke cognitive impairment have not been fully understood yet. We sought to examine the frequency and risk factors of cognitive impairment after ischemic stroke in a large stroke cohort of China. Methods: A total of 434 consecutive patients with ischemic stroke were enrolled. The cognitive status before and 3 months after stroke was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly and the Mini-Mental State Examination, respectively. Poststroke cognitive impairment was defined as cognitive impairment with concomitant stroke, stroke-related cognitive impairment was defined as cognitive impairment developing after index stroke, and cognitive impairment after first-ever stroke was defined as cognitive impairment developing after first-ever stroke. Logistic regression analysis was used to find the risk factors of cognitive impairment after stroke. Results: (1) Frequency of poststroke cognitive impairment was 37.1%, that of stroke-related cognitive impairment was 32.2%, and that of cognitive impairment after first-ever stroke was 29.6%. (2) The patients with cognitive impairment more often had older age, low educational level, atrial fibrillation, prior stroke, everyday drinking, left carotid territory infarction, multiple lesions, embolism, and dysphasia. (3) The factors associated with poststroke cognitive impairment in logistic regression analysis were age (OR 1.215, 95% CI 1.163–1.268), low educational level (OR 2.023, 95% CI 1.171–3.494), prior stroke (OR 5.130, 95% CI 2.875–9.157), everyday drinking (OR 2.013, 95% CI 1.123–3.607), dysphasia (OR 3.994, 95% CI 1.749–9.120), and left carotid territory infarction (OR 2.685, 95% CI 1.595–4.521). Conclusions: Cognitive impairment is common 3 months after ischemic stroke in Chinese people. Risk factors for poststroke cognitive impairment include age, low educational level, everyday drinking, prior stroke, dysphasia, and left carotid territory infarction.
Raynaud’s Phenomenon and Endothelial Dysfunction in End-Stage Renal Disease Patients Treated with Hemodialysis
Authors: Czupryniak Aneta , Kałużyńska Anna , Nowicki Michał , Więcek Bogusław , Bald Edward , Owczarek Danuta
Published: September 2004

Background/Aims: Steal syndrome is a well-known complication of arteriovenous shunt placement. Increased frequency of Raynaud’s phenomenon (RP) especially concerning shunt limb is reported among hemodialysis (HD) patients. The aim of the study was to assess the relation of impairment of peripheral circulation diagnosed with cold stress test (CST) and thermography to the AV shunt location and markers of endothelial dysfunction in HD patients. Methods: The study group comprised 21 patients (6 male, 15 female, mean age 32.6 ± 15.0 years) treated with HD for a mean of 69 ± 54 months. 10 healthy individuals (4 male, 6 female, mean age 38.6 ± 14.7 years) served as controls. The diagnosis of RP was made upon the results of thermographic measurements during CST. Von Willebrand factor activity and antigen, endothelin-1 and plasma total homocysteine (tHcy) were measured in all subjects. Results: RP was found significantly more often in HD patients than in controls: 11/21 vs. 1/10 (p = 0.04). RP occurred in both hands in 7/11 (64%) patients. tHcy was higher in HD patients than in the controls (31.7 ± 13.9 vs. 10.9 ± 3.2 µg/l, p < 0.0001). tHcy and von Willebrand factor antigen were significantly higher in the RP-positive than RP-negative patients or controls. Conclusion: Small vessel dysfunction diagnosed as positive RP is a frequent finding in HD patients. It seems that endothelial injury rather than AV shunt steal syndrome is responsible for development of RP in HD patients.
Monitoring the Cellular Effects of HMG-CoA Reductase Inhibitors In Vitro and Ex Vivo
Authors: Cicha Iwona , Schneiderhan-Marra Nicole , Yilmaz Atilla , Garlichs Christoph D. , Goppelt-Struebe Margarete
Published: September 2004

Objective—Inhibition of 3hydroxy3methylglutaryl–coenzyme A (HMG-CoA) reductase by statins and the subsequent reduction in Rho protein isoprenylation inactivates these important signaling molecules. The purpose of this study was to directly monitor statin effects on Rho proteins.

Methods and Results—We used biphasic Triton X-114 system, 1-dimensional isoelectric focusing, and 2D-electrophoresis for the separation of modified and nonmodified Rho proteins. These methods were evaluated in human fibroblasts treated with simvastatin. 2D-electrophoresis, which proved to be the most sensitive method, revealed 2 major spots of identical molecular weight but different isoelectric points, with the more basic spot representing the carboxymethylated form of RhoA. In control cells, 90% of RhoA was fully modified (carboxymethylated). After treatment with simvastatin, a significant shift toward the unmethylated form was observed, representing inhibition of isoprenylation, which is a prerequisite to further modification. Similar shifts were observed for Rac1 and Cdc42. In freshly isolated peripheral blood mononuclear cells, a shift toward nonmodified RhoA was observed after treatment with atorvastatin in vitro and in vivo. There was a significant increase in unmethylated RhoA in statin-treated individuals versus control individuals.

Conclusions—2D-electrophoresis is a sensitive method for detecting changes in the amount of nonisoprenylated Rho proteins, allowing monitoring the direct cellular effects of statins.
Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Induces Monocyte Adhesion by Stimulating Reactive Oxygen Species Production From a Nox1-Based NADPH Oxidase
Authors: Sorescu George P. , Song Hannah , Tressel Sarah L. , Hwang Jinah , Dikalov Sergey , Smith Debra A. , Boyd Nolan L. , Platt Manu O. , Lassègue Bernard , Griendling Kathy K. , Jo Hanjoong
Published: September 2004

Atherosclerosis is an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions including oscillatory shear stress (OS). OS exposure induces endothelial expression of bone morphogenic protein 4 (BMP4), which in turn may activate intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesion. OS is also known to induce monocyte adhesion by producing reactive oxygen species (ROS) from reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, raising the possibility that BMP4 may stimulate the inflammatory response by ROS-dependent mechanisms. Here we show that ROS scavengers blocked ICAM-1 expression and monocyte adhesion induced by BMP4 or OS in endothelial cells (ECs). Similar to OS, BMP4 stimulated H
2
O
2
and O
2
−
production in ECs. Next, we used ECs obtained from p47phox
−/−
mice (MAE-p47
−/−
), which do not produce ROS in response to OS, to determine the role of NADPH oxidases. Similar to OS, BMP4 failed to induce monocyte adhesion in MAE-p47
−/−
, but it was restored when the cells were transfected with p47
phox
plasmid. Moreover, OS-induced O
2
−
production was blocked by noggin (a BMP antagonist), suggesting a role for BMP. Furthermore, OS increased gp91phox (nox2) and nox1 mRNA levels while decreasing nox4. In contrast, BMP4 induced nox1 mRNA expression, whereas nox2 and nox4 were decreased or not affected, respectively. Also, OS-induced monocyte adhesion was blocked by knocking down nox1 with the small interfering RNA (siRNA). Finally, BMP4 siRNA inhibited OS-induced ROS production and monocyte adhesion. Together, these results suggest that BMP4 produced in ECs by OS stimulates ROS release from the nox1-dependent NADPH oxidase leading to inflammation, a critical early atherogenic step.
Inhibition of Cytochrome P450ω-Hydroxylase
Authors: Nithipatikom Kasem , Gross Eric R. , Endsley Michael P. , Moore Jeannine M. , Isbell Marilyn A. , Falck John R. , Campbell William B. , Gross Garrett J.
Published: September 2004

Cytochrome P450s (CYP) and their arachidonic acid (AA) metabolites have important roles in regulating vascular tone, but their function and specific pathways involved in modulating myocardial ischemia–reperfusion injury have not been clearly established. Thus, we characterized the effects of several selective CYPω-hydroxylase inhibitors and a CYPω-hydroxylase metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), on the extent of ischemia–reperfusion injury in canine hearts. During 60 minutes of ischemia and particularly after 3 hours of reperfusion, 20-HETE was produced at high concentrations. A nonspecific CYP inhibitor, miconazole, and 2 specific CYPω-hydroxylase inhibitors, 17-octadecanoic acid (17-ODYA) and N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), markedly inhibited 20-HETE production during ischemia–reperfusion and produced a profound reduction in myocardial infarct size (expressed as a percent of the area at risk) (19.6±1.7% [control], 8.4±2.5% [0.96 mg/kg miconazole], 5.9±2.2% [0.28 mg/kg 17-ODYA], and 10.8±1.8% [0.40 mg/kg DDMS],
P
<0.05, respectively). Conversely, exogenous 20-HETE administration significantly increased infarct size (26.9±1.9%,
P
<0.05). Several CYPω-hydroxylase isoforms, which are known to produce 20-HETE such as CYP4A1, CYP4A2, and CYP4F, were demonstrated to be present in canine heart tissue and their activity was markedly inhibited by incubation with 17-ODYA. These results indicate an important endogenous role for CYPω-hydroxylases and in particular their product, 20-HETE, in exacerbating myocardial injury in canine myocardium. The full text of this article is available online at http://circres.ahajournals.org.
Microembolic Signals Detected by Transcranial Doppler Sonography During Carotid Endarterectomy and Correlation With Serial Diffusion-Weighted Imaging
Authors: Wolf Oliver , Heider Peter , Heinz Marco , Poppert Holger , Sander Dirk , Greil Oliver , Weiss Wolfgang , Hanke Marc , Eckstein Hans-Henning
Published: September 2004

Background and Purpose—

Embolic events are a major cause for procedure-related strokes after carotid endarterectomy (CEA). Transcranial Doppler sonography can reveal embolic events as microembolic signals (MES) during CEA. MES during declamping and shunting are frequently detected. MES during shunting are rare and known to be correlated with the neurological outcome of the patient. In the present study, we analyzed the occurrence of MES within different stages of CEA and whether MES within those stages were correlated with cerebral ischemia, as detected by diffusion-weighted imaging (DWI), and brain infarction, as detected by contrast-enhanced MRI.

Methods—

Thirty-three patients were monitored intraoperatively for MES using transcranial Doppler sonography. DWI was performed within 24 hours before and after surgery. Positive postoperative DWI led to reexamination with contrast-enhanced T1-MRI 7 to 10 days after CEA for detection of cerebral infarction.

Results—

MES were detected in 32 of 33 patients. The highest number of MES was found during shunting and declamping. A significant correlation was found between MES and DWI-lesions during dissection. A significant correlation was found between MES during dissection and shunting, and nonsignificant correlation was found between MES and the occurrence of cerebral infarction.

Conclusion—

MES could be regularly detected during CEA. Dissection and shunting seem to be the most vulnerable stages of the procedure.