bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of oxyhemoglobin affinity in patients with obstructive sleep apnea-hypopnea syndrome without daytime hypoxemia
Authors: Clause Didier , Detry Bruno , Rodenstein Daniel , Liistro Giuseppe
Published: October 2008

A decrease in hemoglobin affinity for oxygen is considered an adaptive mechanism against tissue hypoxia. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by recurrent episodes of apnea and hypopnea resulting in arterial oxygen desaturations during sleep. Maillard et al. ( 10 ) observed a right shift of the oxyhemoglobin dissociation curve (ODC) and an increase in 2,3-diphosphoglycerate (2,3-DPG) concentration ([2,3-DPG]) in 15 patients with severe OSAHS, but some had slight daytime arterial hypoxemia while breathing room air. The aim of our study was to measure the ODC and 2,3-DPG concentrations in a group of subjects normoxemic during daytime referred to our sleep laboratory for suspicion of snoring or OSAHS. The patients were recruited during a period of 6 mo. All arterial and venous blood samples were taken early in the morning within 1 h of awakening following a full-night polysomnography. ODC and 2,3-DPG were analyzed in 88 patients: 56 OSAHS (oxygen desaturation index: 27.5 ± 24.5) and 32 non-OSAHS. We found a significant correlation between the P50 and 2,3-DPG levels in the 88 patients: r = 0.502, P < 0.001. We observed no difference between OSAHS and non-OSAHS for the P50 and for [2,3-DPG]. There was no correlation between the severity of OSAHS and either P50 or [2,3-DPG]. Finally, there was no change in these parameters measured at baseline, after 3 days and after 1 mo of treatment by nasal continuous positive airway pressure in 7 patients with OSAHS. We conclude that patients with OSAHS who are normoxemic during daytime have comparable oxyhemoglobin affinity than nonapneic subjects.
Effect of physical training on function of chronically painful muscles: a randomized controlled trial
Authors: Andersen Lars L. , Andersen Christoffer H. , Zebis Mette K. , Nielsen Pernille K. , Søgaard Karen , Sjøgaard Gisela
Published: October 2008

Pain and tenderness of the upper trapezius muscle is frequent in several occupational groups. The objective of this study is to investigate the effect of three contrasting interventions on muscle function and pain in women with trapezius myalgia. A group of employed women ( n = 42) with a clinical diagnosis of trapezius myalgia participated in a 10-wk randomized controlled intervention: specific strength training of the neck/shoulder muscles, general fitness training performed as leg bicycling, or a reference intervention without physical activity. Torque and electromyography (EMG) were recorded during maximal shoulder abductions in an isokinetic dynamometer at −60, 60, 0, and 180°/s. Furthermore, a submaximal reference contraction with only the load of the arms was performed. Significant changes were observed only in the specific strength training group. Pain decreased by 42–49% ( P < 0.01–0.05). Whereas the EMG activity of the unaffected deltoid remained unchanged during the maximal contractions, an increase in EMG amplitude (42–86%; P < 0.001–0.05) and median power frequency (19%; P < 0.001) were observed for the painful trapezius muscle. Correspondingly, torque increased by 18–53% ( P < 0.001–0.05). EMG during the reference contraction decreased significantly for both the trapezius and deltoid muscles ( P < 0.01). In conclusion, specific strength training relieves pain and increases maximal activity specifically of the painful trapezius muscle, leading to increased shoulder abduction strength in women with trapezius myalgia. Furthermore, decreased relative workload may indirectly augment pain reduction.
Genome-Wide Analysis of Dietary Eicosapentaenoic Acid- and Oleic Acid-Induced Modulation of Colon Inflammation in Interleukin-10 Gene-Deficient Mice
Authors: Knoch Bianca , Barnett Matthew P.G. , Zhu Shuotun , Park Zaneta A. , Nones Katia , Dommels Yvonne E.M. , Knowles Scott O. , McNabb Warren C. , Roy Nicole C.
Published: October 2008

Background/Aims: Dietary n–3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient (Il10–/–) mice. Methods: At 35 days of age, 12 weaned Il10–/– and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n–3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. Results: In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed Il10–/– compared to C57 mice. Il10–/– mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in Il10–/– mice. Conclusions: These data indicate that dietary EPA-induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the Ppara gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins.
A Rare Case of Posterior Urethral Valve and Pleural Effusion in Down Syndrome with Successful Intrauterine Shunt
Authors: Kim Ari , Park In Yang , Young Lee , Shin Jong Chul
Published: October 2008

Posterior urethral valve or pleural effusion accompanied with Down syndrome have been described previously; however, there is no reported case of posterior urethral valve and pleural effusion with Down syndrome. A 45-year-old multigravida woman was transferred due to bilateral fetal hydrothorax, polyhydramnios, and threatened preterm labor at 32 weeks’ gestation. Transabdominal ultrasonography revealed additional abnormality, posterior urethral valve. Amniocentesis was repeated due to intense amniotic fluid and patient’s dyspnea. Ultrasound-guided thoracoamniotic shunt and vesicoamniotic shunt were done successfully. At 33 weeks’ gestation, intrauterine infection was suspected by the laboratory findings of amniotic fluid. A 2.25-kg male baby with characteristic phenotypic findings of Down syndrome was delivered by Cesarean section. Cytogenetic analysis after birth revealed a karyotype of 47,XY,+21. The present case reinforces the notions that fetuses with multiple anomalies, like congenital pleural effusion and posterior urethral valve, are at risk of chromosomal abnormalities, in spite of their low possibilities of association with chromosomal abnormalities.
A Case of Disseminated Peritoneal Leiomyomatosis Developing after Laparoscope-Assisted Myomectomy
Authors: Miyake Takahito , Enomoto Takayuki , Ueda Yutaka , Ikuma Kenichiro , Morii Eiichi , Matsuzaki Shinya , Murata Yuji
Published: October 2008

A 36-year-old nulliparous woman developed multiple extra-uterine fibroids in the pelvic cavity years after laparoscopic myomectomy. Molecular genetic analysis by methylation-specific polymerase chain reaction (MSPCR) of the human X-linked androgen receptor gene and loss of heterozygosity (LOH) analysis at 5 microsatellite loci was performed on the tumors. All tumors showed an identical non-random X-chromosome inactivation pattern by MSPCR and an identical pattern of LOH was found in all the tumors by LOH analysis. This demonstrated that 3 fibroids resected 2 years later and 14 fibroids resected 6 years later were all metastatic tumors originating from the uterine leiomyoma found during the initial surgery, suggesting that morcellation before removal of the leiomyoma nodule during laparoscopic myomectomy may have been associated with the pathogenesis of this case.
Histopathological Features of Patients with Chronic Pancreatitis due to Mutations in the PRSS1 Gene: Evaluation of BRAF and KRAS2 Mutations
Authors: Felderbauer Peter , Stricker Ingo , Schnekenburger Jürgen , Bulut Kerem , Chromik Ansgar M. , Belyaev Orlin , Muller Christophe A. , Uhl Waldemar , Tannapfel Andrea , Schmidt Wolfgang E.
Published: October 2008

Background/Aims: Hereditary pancreatitis (HP) is a rare cause of chronic pancreatitis (CP; 1%) and more than 25 mutations in the PRSS1 gene have been detected. HP patients with the p.R122H mutation have a 35% lifetime risk of developing pancreatic cancer, but the oncogenetic process remains unknown. We have investigated the histopathological features and frequency of BRAF and KRAS2 mutations in 2 patients with PRSS1 mutations (p.A121T, p.R122H) and patients with CP (n = 11). Methods: Pancreatic tissue was stained with hematoxylin-eosin and examined by light microscopy. Mutational analysis of the BRAF (exon 5, 11) and KRAS2 (exon 1) genes was performed using PCR and direct DNA sequencing. Results: Histopathological features revealed similar results in both patients, pancreata showed strong fibrosis and ducts with signs of distortion, irregular size and noticeable dilatations. We identified one BRAF mutation (p.V600E) in the p.R122H patient and two KRAS2 (p.G12D; p.G12C) mutations in CP controls. Conclusions: Our results sustain the knowledge about the clinical phenotype of patients with PRSS1 mutations who have a high risk of pancreatic cancer. Whether the histopathological picture or the BRAF mutation is specific for patients with PRSS1 mutations or plays a specific role in the tumorigenesis of patients with HP needs to be further evaluated.
Depression after First-Ever Ischemic Stroke: The Prognostic Role of Neuroanatomic Subtypes in Clinical Practice
Authors: Provinciali Leandro , Paolucci Stefano , Torta Riccardo , Toso Vito , Gobbi Beatrice , Gandolfo Carlo
Published: October 2008

Background: The relationship between poststroke depression (PSD) and Oxford Community Stroke Project (OCSP) subtypes is uncertain. Methods: 713 first-ever ischemic stroke patients recruited in a multicenter investigation to evaluate prevalence, onset time and severity of PSD. Stroke subtypes were considered as independent predictors of PSD occurrence by logistic regression. Results: Results showed similar prevalence of PSD in stroke subtypes with the exception of TACI. Only patients with total anterior cerebral ischemia (TACI) showed a higher PSD occurrence (OR: 1.76, CI: 1.14–2.71). Multivariate analysis underlined the role of severe functional impairment, previous depressive disorders and female sex. Neither the OCSP subgroups, nor left and right involvement were predictive of PSD. TACI and left-sided strokes were related to higher depression severity scores. Conclusions: In clinical practice, the definition of neuroanatomic subtypes provides little contribution specifically to PSD prediction after a first-ever ischemic stroke.
Accuracy and Anatomical Coverage of Perfusion CT Assessment of the Blood-Brain Barrier Permeability: One Bolus versus Two Boluses
Authors: Dankbaar Jan Willem , Hom Jason , Schneider Thomas , Cheng Su-Chun , Lau Benison C. , van der Schaaf Irene , Virmani Sunny , Pohlman Scott , Dillon William P. , Wintermark Max
Published: October 2008

Purpose: To assess whether blood-brain barrier permeability (BBBP) values, extracted with the Patlak model from the second perfusion CT (PCT) contrast bolus, are significantly lower than the values extracted from the first bolus in the same patient. Materials and Methods: 125 consecutive patients (29 with acute hemispheric stroke and 96 without stroke) who underwent a PCT study using a prolonged acquisition time up to 3 min were retrospectively identified. The Patlak model was applied to calculate the rate of contrast leakage out of the vascular compartment. Patlak plots were created from the arterial and parenchymal time enhancement curves obtained in multiple regions of interest drawn in ischemic brain tissue and in nonischemic brain tissue. The slope of a regression line fit to the Patlak plot was used as an indicator of BBBP. Square roots of the mean squared errors and correlation coefficients were used to describe the quality of the linear regression model. This was performed separately for the first and the second PCT bolus. Results from the first and the second bolus were compared in terms of BBBP values and the quality of the linear model fitted to the Patlak plot, using generalized estimating equations with robust variance estimation. Results: BBBP values from the second bolus were not lower than BBBP values from the first bolus in either nonischemic brain tissue [estimated mean with 95% confidence interval: 1.42 (1.10–1.82) ml·100 g–1·min–1 for the first bolus versus 1.64 (1.31–2.05) ml·100 g–1·min–1 for the second bolus, p = 1.00] or in ischemic tissue [1.04 (0.97–1.12) ml·100 g–1·min–1 for the first bolus versus 1.19 (1.11–1.28) ml·100 g–1·min–1 for the second bolus, p = 0.79]. Compared to regression models from the first bolus, the Patlak regression models obtained from the second bolus were of similar or slightly better quality. This was true both in nonischemic and ischemic brain tissue. Conclusion: The contrast material from the first bolus of contrast for PCT does not negatively influence measurements of BBBP values from the second bolus. The second bolus can thus be used to increase anatomical coverage of BBBP assessment using PCT.
Analyzing Fatal Cases of Chinese Patients with Primary Antineutrophil Cytoplasmic Antibodies-Associated Renal Vasculitis: A 10-Year Retrospective Study
Authors: Chen Yong-Xi , Yu Hai-Jin , Zhang Wen , Ren Hong , Chen Xiao-Nong , Shen Ping-Yan , Xu Yao-Wen , Li Xiao , Pan Xiao-Xia , Ni Li-Yan , Wang Wei-Ming , Chen Nan
Published: October 2008

Background/Aims: Primary antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) used to have poor prognosis, and renal involvement is its most common manifestation. Few studies have been published focusing on AASV patients with poor prognosis. Methods: From 1997 to 2006, 101 patients with ANCA-associated renal vasculitis (70 microscopic polyangiitis, MPA; 14 Wegener’s granulomatosis, WG; 3 Churg-Strauss syndrome, CSS; 14 renal limited vasculitis, RLV) were diagnosed in Shanghai Ruijin Hospital and 26 deaths were recorded among them. Patients’ data were retrospectively analyzed. Results: Patients with WG, MPA and RLV made up for 23.1% (6/26), 65.4% (17/26) and 11.5% (3/26) of all deaths. No deaths were observed among CSS patients. Infection alone accounted for 13 deaths. Infection together with pulmonary involvement of active vasculitis accounted for 3. Organ-specific involvement of active vasculitis alone caused 8 deaths. Others died of acute myocardial infarction or gastric carcinoma. Compared with patients who survived, nonsurvivors had more severe renal insufficiency and older age (p < 0.01). There was no significant difference regarding clinical presentation at diagnosis and cause of death between patients who survived first remission-induction treatment and those who did not. Infection remained the major cause of death. Conclusion: Infection is the major cause of death in patients with ANCA-associated renal vasculitis, and treatment response might not correlate to severity of disease in patients with poor prognosis. Rational use of immunosuppressants could improve the prognosis.
Development of a Speaker Discrimination Test for Cochlear Implant Users Based on the Oldenburg Logatome Corpus
Authors: Mühler Roland , Ziese Michael , Rostalski Dorothea
Published: October 2008

The purpose of the study was to develop a speaker discrimination test for cochlear implant (CI) users. The speech material was drawn from the Oldenburg Logatome (OLLO) corpus, which contains 150 different logatomes read by 40 German and 10 French native speakers. The prototype test battery included 120 logatome pairs spoken by 5 male and 5 female speakers with balanced representations of the conditions ‘same speaker’ and ‘different speaker’. Ten adult normal-hearing listeners and 12 adult postlingually deafened CI users were included in a study to evaluate the suitability of the test. The mean speaker discrimination score for the CI users was 67.3% correct and for the normal-hearing listeners 92.2% correct. A significant influence of voice gender and fundamental frequency difference on the speaker discrimination score was found in CI users as well as in normal-hearing listeners. Since the test results of the CI users were significantly above chance level and no ceiling effect was observed, we conclude that subsets of the OLLO corpus are very well suited to speaker discrimination experiments in CI users.
Paroxysmal Non-Kinesigenic Dyskinesia Caused by the Mutation of MR-1 in a Large Polish Kindred
Authors: Friedman Andrzej , Zakrzewska-Pniewska Beata , Domitrz Izabela , Lee Hsien-Yang , Ptacek Louis , Kwiecinski Hubert
Published: October 2008

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a clinical syndrome of sudden involuntary movements, mostly of dystonic type, which may be triggered by alcohol or coffee intake, stress and fatigue. The attacks of PNKD may consist of various combinations of dystonia, chorea, athetosis and balism. They can be partial and unilateral, but mostly the hyperkinetic movements are bilateral and generalized. We present a large Polish family with 7 symptomatic members of the family in 6 generations. In all affected persons, the onset of clinical symptoms was in early childhood. All male cases showed an increase in severity and frequency of the attacks with ageing, while the only living female patient noticed an improvement of PNKD during both her pregnancies and also after menopause. In addition, at the age of 55 years, she developed symptoms of Parkinson’s disease with good response to levodopa treatment.
A Case of Cronkhite-Canada Syndrome: Remission after Treatment with Anti-Helicobacter pylori Regimen
Authors: Okamoto Kenta , Isomoto Hajime , Shikuwa Saburo , Nishiyama Hitoshi , Ito Masahiro , Kohno Shigeru
Published: October 2008

A 67-year-old man with nausea, appetite loss, frequent diarrhea and severe weight loss presented with alopecia, skin hyperpigmentation and onychodystrophy. Laboratory investigations showed mild anemia, hypoproteinemia and hypoalbuminemia. Colonoscopy identified the numerous, hyperemic and sessile polyps with mucous exudation of various sizes throughout the colorectum. The ileocecal valve was substantially swollen. Magnified chromoendoscopy revealed sparsely distributed crypt openings with widening of the preicryptal space without destruction in the affected lesions. Upper gastrointestinal endoscopy revealed multiple small, reddish, and sessile polyps in the duodenum and Helicobacter pylori-associated gastritis. Histopathological examination of the colonic polyps revealed cystic dilatation and elongation of scattered glands with epithelial hyperplasia and stromal edema and inflammatory cell infiltrates. Thus, a diagnosis of Cronkhite-Canada syndrome was made. The patient was given clarithromycin, amoxicillin and lansoprazole, resulting in negative 13C-urea breath tests. Three months later, his clinical symptoms and edema of the legs resolved with normalization of serum total protein and albumin levels and return to his previous body. The ectodermal abnormalities were resolved 8 months later. On repeat colonoscopic examinations, there was progressive remission of the duodenal and colorectal polyposis, leaving scattered pedunculated polyps in the transverse and ascending colon and on the almost normal-appearing ileocecal valve. At the follow-up magnifying endoscopic examination 8 months later, small round or round-oval pits were densely and regularly distributed.
Carnitine Status in Early-Treated Children, Adolescents and Young Adults with Phenylketonuria on Low Phenylalanine Diets
Authors: Weigel C. , Kiener C. , Meier N. , Schmid P. , Rauh M. , Rascher W. , Knerr I.
Published: October 2008

Background: In patients with phenylketonuria (PKU), the carnitine status may be impaired for metabolic or dietary reasons, including low carnitine intake, a deficient synthesis and acylcarnitine production from phenylalanine (Phe) metabolites. Methods: Free carnitine and acylcarnitine status was assessed in 30 PKU patients, aged 0.5–36 years, mean age 13.8 years. Our cohort was divided into 2 groups according to the preparations of Phe-free amino acids (AA) prescribed, with or without carnitine supplementation. Daily Phe intake, dosage of AA mixtures and body weight were recorded along with measurements of acylcarnitines in blood spots (by tandem mass spectrometry) and serum AA. Control data were obtained from 50 healthy volunteers (aged 0.2–39 years, mean age 14.2. years). Statistical analysis comprised the t test, ANOVA and Pearson’s correlation. Results: PKU patients had lower free carnitine (C0) concentrations than controls (25.82 ± 7.38 vs. 31.28 ± 6.17 µmol/l; p < 0.001) and lower octanoyl- and decanoylcarnitine. Mean C0 and acylcarnitine concentrations did not differ between PKU patients taking the various protein substitutes with or without carnitine; mean C0 levels in PKU patients receiving AA enriched with carnitine were still lower compared with controls (p < 0.05). Conclusions: Actual dietary regimens can not completely normalize the carnitine status; therefore, carnitine levels should be given careful consideration in subjects with PKU.
Change of Epigenetic Control of Cystathionine Beta-Synthase Gene Expression through Dietary Vitamin B12 Is Not Recovered by Methionine Supplementation
Authors: Uekawa Atsushi , Katsushima Keishuke , Ogata Asumi , Kawata Tetsunori , Maeda Nozomi , Kobayashi Ken-Ichi , Maekawa Akio , Tadokoro Tadahiro , Yamamoto Yuji
Published: October 2008

Background/Aims: Vitamin B12 (B-12) is an essential cofactor for methionine synthase, and methionine is critical for the methylation of various biological molecules including DNA. Whether changes in B-12 levels can alter specific gene expression through DNA methylation and whether dietary methionine has any effect on general DNA methylation status still remains controversial. Methods: We raised severely B-12-deficient rats as well severely-B-12 deficient rats but supplemented with 5% methionine. mRNA levels of methionine cycle-related enzymes were analyzed. Results: Gene expression patterns changed under B-12-deficient conditions but were recovered by dietary methionine supplementation to B-12-deficient rats. However, cystathionine β-synthase mRNA levels, which had decreased under B-12-deficient conditions, did not recover with supplementary dietary methionine. The CpG island of the cystathionine β-synthase promoter was hypomethylated in B-12-deficient rats, and showed no recovery after methionine addition. Conclusions: Dietary B-12 can affect epigenetic machinery by regulating DNA methylation status and dietary methionine may have small effects on DNA methylation.
Impact of Delayed Arterial Cord Blood Sampling for Lactate Assay
Authors: Dessolle Lionel , Lebrec Jeremie , Daraï Emile
Published: October 2008

Background: Umbilical cord sampling at delivery provides important data on the newborn’s metabolism. Objective: To evaluate the impact of delayed sampling on arterial cord blood lactate values. Methods: Observational study of 168 consecutive deliveries at a tertiary teaching hospital. Arterial cord blood lactate was determined with a test strip method on paired samples obtained immediately and 5–30 min after birth. At least 90 paired measurements were necessary to show a difference in lactate levels of ≥0.5 mmol/l between the first and second samples. Lactate levels according to the time interval between birth and sampling. Results: One hundred and two paired samples were available for analysis. The lactate value was always higher in the second sample than in the first. Lactate levels increased linearly with time, by 0.062 mmol/l per min. The degree of increase was independent of the initial lactate level and the route of delivery. Delayed sampling resulted in abnormal lactate levels in 16% of neonates born with normal lactate levels. Conclusions: Our results show that delayed sampling of arterial cord blood is unreliable for neonatal lactate assay. Cord blood sampling and lactate assay should therefore be performed immediately after delivery.
Styrene Maleic Acid-Pirarubicin Disrupts Tumor Microcirculation and Enhances the Permeability of Colorectal Liver Metastases
Authors: Daruwalla Jurstine , Greish Khaled , Malcontenti-Wilson Cathy , Muralidharan Vijayaragavan , Iyer Arun , Maeda Hiroshi , Christophi Chris
Published: October 2008

Background: Doxorubicin is a commonly used chemotherapy limited by cardiotoxicity. Pirarubicin, derived from doxorubicin, selectively targets tumors when encapsulated in styrene maleic acid (SMA), forming the macromolecular SMA pirarubicin. Selective targeting is achieved because of the enhanced permeability and retention (EPR) effect. SMA-pirarubicin inhibits the growth of colorectal liver metastases, but tumor destruction is incomplete. The role played by the tumor microcirculation is uncertain. This study investigates the pattern of microcirculatory changes following SMA-pirarubicin treatment. Methods: Liver metastases were induced in CBA mice using a murine-derived colon cancer line. SMA-pirarubicin (100 mg/kg total dose) was administered intravenously in 3 separate doses. Twenty-four hours after chemotherapy, the tumor microvasculature was examined using CD34 immunohistochemistry and scanning electron microscopy. Tumor perfusion and permeability were assessed using confocal in vivo microscopy and the Evans blue method. Results: SMA-pirarubicin reduced the microvascular index by 40%. Vascular occlusion and necrosis were extensive following treatment. Viable cells were arranged around tumor vessels. Tumor permeability was also increased. Conclusion: SMA-pirarubicin damages tumor cells and the tumor microvasculature and enhances tumor vessel permeability. However, tumor necrosis is incomplete, and the growth of residual cells is sustained by a microvascular network. Combined therapy with a vascular targeting agent may affect residual cells, allowing more extensive destruction of tumors.
Decreased Vitreal Hyaluronan Levels with Aging
Authors: Itakura Hirotaka , Kishi Shoji , Kotajima Nobuo , Murakami Masami
Published: October 2008

Purpose: To investigate age-related changes in hyaluronan levels in human eyes before and after vitrectomy surgery, we measured the hyaluronan levels in the vitreous samples obtained during vitrectomy and postoperative fluid-air exchange. Methods: We obtained the vitreous during vitrectomy from 26 eyes of 26 patients with macular hole (MH) and 52 eyes of 52 patients with diabetic retinopathy (DR). After vitrectomy, we collected fluid samples during fluid-air exchange from 6 eyes with MH and 9 eyes with DR. The hyaluronan level was measured by the sandwich binding protein assay. Results: In the vitreous of the 54 eyes (26 eyes with MH and 28 eyes with DR and no vitreous hemorrhage), hyaluronan levels significantly decreased with patient age (r = –0.66, p < 0.00000005). Hyaluronan levels in postoperative vitreous fluid were significantly lower in 6 eyes with MH (p < 0.05) and 9 eyes with DR (p < 0.01) than those obtained during vitrectomy. Conclusions: There was a significant decrease in vitreous hyaluronan with aging. High-molecular-weight hyaluronan appears not to be formed in vitreous fluid after vitrectomy.
Low Plasma Activated Protein C-Protein C Inhibitor Complex Concentration Is Associated with Vascular Access Failure in Hemodialysis Patients
Authors: Bakoush Omran , Öhlin Ann-Kristin , Strandberg Karin , Kurkus Jan
Published: October 2008

Background: Vascular access failure is a common cause of morbidity in patients with end-stage renal failure on hemodialysis (HD). Activation of the coagulation system and formation of a thrombus play important roles in recurrent arteriovenous fistula/graft (AVFG) failure. Thrombin in complex with thrombomodulin (TM) activates the anticoagulant protein C and creates activated protein C (APC), which is subsequently inactivated by the protein C inhibitor (PCI). The plasma concentration of the complex between APC and PCI (P-APC-PCI complex) is increased in hypercoagulable states and is therefore a sensitive indicator of the degree of activation of blood coagulation. Methods: Thirty-five HD patients dialyzed through a functioning AVFG were studied. The period of patency of AVFGs was recorded. Blood was drawn before and after the HD session for the analysis of the APC-PCI complex, soluble TM concentration and activity, von Willebrand factor antigen and homocysteine. Results: Patients with frequent AVFG failures (n = 8) had a significantly lower level of P-APC-PCI complex (median 0.09 µg/l) than those with less frequent AVFG failures (median 0.18 µg/l; n = 27; p = 0.04). No other significant differences were found between the groups. Conclusion: Thus, a low level of P-APC-PCI complex may be associated with an increased risk of AVFG failure in HD patients. Further prospective studies are needed to confirm these results and to evaluate the possibility of prophylactic measures.
Cystatin C or Creatinine for Detection of Stage 3 Chronic Kidney Disease in Anorexia Nervosa
Authors: Delanaye Pierre , Cavalier Etienne , Radermecker Régis P. , Paquot Nicolas , Depas Gisèle , Chapelle Jean-Paul , Scheen André J. , Krzesinski Jean-Marie
Published: October 2008

Background: Patients with anorexia nervosa (AN) are at a high risk of renal failure. Chronic kidney disease (CKD) is often missed in these patients because the serum creatinine is a poor marker of kidney function. We studied the utility of cystatin C to detect renal failure in this population. Method: Twenty-seven AN patients were studied. Glomerular filtration rates (GFR) were measured with the chromium-51- ethylenediaminetetraacetate (51Cr-EDTA) method. We compared the ability of creatinine and cystatin C to detect stage 3 CKD (GFR below 60 ml/min) by ROC curve analysis. Results: In this cohort, there is no correlation between GFR and serum creatinine, but there is a significant correlation between cystatin C and GFR. By ROC analysis, the cystatin C concentration is better than the serum creatinine concentration for the detection of stage 3 CKD (area under the curve of 0.86 vs. 0.61, p = 0.05). Conclusion: Plasma cystatin C is better than serum creatinine in detecting stage 3 CKD in patients with AN.
Predictors of Plasmodium vivax Malaria-Induced Nephropathy in Young Korean Men
Authors: Chung Byung Ha , Lee Sei Won , Lee Sang Eun , Hwang Tae Jun , Shin Ho Sik
Published: October 2008

Background:Plasmodium vivax malaria accounts for more than half of all malaria cases in Asia and Latin America. Despite the high prevalence of disease caused by this parasite, research into its effects (especially its renal effect) has lagged disproportionately. To investigate predictors of vivax malaria-induced nephropathy, we analyzed the cases of vivax malaria-induced nephropathy in young Korean men. Methods: This was a retrospective analysis of P. vivax patients with acute nephropathy (all males, n = 75), defined by an absolute increase in serum creatinine of 0.3 mg/dl or more (equal to an estimated glomerular filtration rate (eGFR) <80 ml/min) (group 1, n = 31) or proteinuria (group 2, n = 44), between January 2004 and December 2007. The eGFR was calculated using a simplified Modification of Renal Disease (MDRD) equation. None of the patients had a history of traveling abroad, drug abuse or blood transfusion. The clinical manifestations, laboratory abnormalities and predictors of nephropathy were reviewed. Results: Out of 398 cases of vivax malaria, 75 patients (all males) suffered from to vivax malaria-induced acute nephropathy. The mean age of the patients who were divided into two groups was 22.8 ± 3.7 and 21.6 ± 1.8 years, respectively (p = 0.089). In group 1, the total serum bilirubin significantly correlated with serum creatinine and eGFR (p = 0.004 and 0.035, correlation coefficient = 0.508 and –0.387, respectively). In group 2, 24-hour proteinuria significantly correlated with hemoglobin (p = 0.004, correlation coefficient = –0.424). Conclusion: Total serum bilirubin (group 1, an absolute increase in serum creatinine of 0.3 mg/dl or more (equal to an eGFR <80 ml/min)) and hemoglobin (group 2, proteinuria) are useful to predict vivax-induced nephropathy.
The effects of exercise capacity and sedentary lifestyle on haemostasis among middle-aged women with coronary heart disease
Authors: Janszky Imre , Eriksson-Berg Margita , Al-Khalili Faris , Schenck-Gustafsson Karin , Nagy Edit
Published: October 2008

Previous studies have established a link/relationship between haemostatic factors and increased risk of cardiovascular disease. In addition, physical conditioning is associated with lower coronary heart disease risk. The purpose of this study was to assess the association between physical exercise and haemostatic factors among middle-aged women surviving an acute coronary event. The Stockholm Female Coronary Risk Study included 292 women aged < 65 years, resident in the greater Stockholm area, who were hospitalized for an acute coronary syndrome. Extensive clinical screening including exercise testing, and blood tests were performed 3–6 months after the coronary event. Self-reported physical activity was assessed by a WHO questionnaire. Patients on warfarin treatment were excluded from our analyses. Haemostatic factors were generally higher among physically inactive patients when compared to physically active women in our univariate models. Exercise capacity had a statistically significant relationship with factor VII antigen (p=0.039) and vWFag (p=0.038) even in our multiadjusted analyses. Physical inactivity and poor physical fitness are associated with a potentially prothrombotic blood profile in middle aged women with coronary heart disease.
Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells
Authors: Tamari Tal , Brenner Benjamin , Aharon Anat
Published: October 2008

Microvesicles (MVs) which include microparticles (MPs) and exosomes are found in blood circulation in normal physiologic conditions and are increased in a variety of diseases. This study evaluated the effects of MVs on human umbilical vein endothelial cells (HUVEC) by morphologic changes, apoptosis, and thrombogenicty, in vitro. Stimulation of monocyte cell line (THP-1) by starvation or by endotoxin and calcium ionophore A23187 resulted in the release of MVs which express exosome marker Tsg 101, negative phospholipids in their leaflets, monocyte markers (CD18, CD14) and active tissue factor (TF). MVs were found to disrupt EC integrity and rapidly induce membrane blebbing. Brief exposure (2–4 hours) to MVs resulted in EC membrane phospholipids “flip-flop” while longer stimulation (20 hours) led to two contradicting outcomes – tube formation as well as apoptosis, as assessed by nuclear fragmentation. Additionally, MVs exposure resulted in increased cell surface thrombogenicity and perturbation of the endothelial haemostatic balance, which were enhanced during longer exposure time. Activity, antigen level and mRNA expression of the coagulation initiator TF were elevated due to (i) adherence of MVs derived TF to the EC membrane, and (ii) an increase in endothelial TF expression. Furthermore, levels of the anticoagulant tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) were decreased. These findings demonstrate that monocyte MVs increase endothelial thrombogenicity and apoptosis. In addition, they induce tube formation which may indicate their angiogenic effect. These findings may clarify, in part, the role of MVs in EC dysfunction associated with inflammatory diseases and hypercoagulable states.
Subclinical hyperthyroidism seems not to have a significant impact on systemic anticoagulation in patients with coumarin therapy
Authors: Naubereit Anna , Joe Alexius Y. , Ezziddin Samer , Biermann Kim , Risse Jörn , Palmedo Holger , Oldenburg Johannes , Biersack Hans-Jürgen , Bucerius Jan
Published: October 2008

There is little data regarding the impact of subclinical hyperthyroidism on coagulation metabolism in patients undergoing systemic anticoagulation therapy with coumarin derivates. In this retrospective analysis we studied 233 patients with benign thyroid disorders receiving therapeutic iodine-131, as well as concomitant systemic anticoagulation therapy (subclinical hyperthyroidism: n=178; overt hyperthyroidism: n=15; euthyroidism: n=40). Multivariate regression analyses were performed in the total study population as well as in the subgroup of patients with subclinical hyperthyroidism to identify the possible impact of several variables on anticoagulation therapy, large enough to push the International Normalized Ratio (INR) level out of the therapeutic range (INR <2.0 or >3.0).Therapy with antibiotics or nitrates was significantly associated with INR-values >3.0 in the total population, while ACE inhibitors were associated with lower incidence of INR-values <2.0. In patients with subclinical hyperthyroidism, therapy with antibiotics was predictive of INR-values >3.0, whereas therapy with thyroid suppressive drugs or TSH-values <0.1 mU/l was associated with INR-values <2.0. Moreover, in a subgroup of 40 patients with the positive history of both subclinical hyperthyroidism and euthyroidism intraindividual comparison with regard to the possible impact on anticoagulation therapy was performed which failed to show any significant differences in INR-values between the two thyroid metabolic conditions. In conclusion, subclinical hyperthyroidism seems to have no significant impact on coagulation metabolism in patients receiving anticoagulation therapy.
γA/γ’ fibrinogen inhibits thrombin-induced platelet aggregation
Authors: Lovely Rehana S. , Rein Chantelle M. , White Tara C. , Jouihan Sari A. , Boshkov Lynn K. , Bakke Antony C. , McCarty Owen J. , Farrell David H.
Published: October 2008

The minor γA/γ’ fibrinogen isoform contains a high affinity binding site for thrombin exosite II that is lacking in the major γA/γA fibrinogen isoform. We therefore investigated the biological consequences of the γ’ chain binding to thrombin. Thrombin-induced platelet aggregation was inhibited by γA/γ’ fibrinogen.Carboxyl terminal peptide fragment γ’410–427 from the γ’ chain was also inhibitory, with an IC50 of ∼200 µM in whole plasma. Deletion of the peptide from either the amino or carboxyl end significantly decreased inhibition. In contrast to thrombin-induced platelet aggregation, aggregation induced by epinephrine, ADP, arachidonic acid, or SFLLRN peptide showed little inhibition by the γ’ peptide. The inhibition of thrombin-induced platelet aggregation was not due to direct inhibition of the thrombin active site, since cleavage of a small peptidyl substrate was 91% of normal even in the presence of 1 mM γ’410–427.The γ’410–427 peptide blocked platelet adhesion to immobilized thrombin under both static and flow conditions,blocked soluble thrombin binding to platelet GPIbα, and inhibited PAR1 cleavage by thrombin. These results suggest that the γ’ chain of fibrinogen inhibits thrombin-induced platelet aggregation by binding to thrombin exosite II. Thrombin that is bound to the γ’ chain is thereby prevented from activating platelets, while retaining its amidolytic activity.
Analysis of platelet α2-adrenergic receptor activity in stable coronary artery disease patients on dual antiplatelet therapy
Authors: Vargová Katarína , László Ádám , Masszi Tamás , Kerecsen Gábor , Préda István , Kiss Róbert Gábor , Béres Bernát János , Tóth-Zsámboki Emese
Published: October 2008

Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure. Alpha-2 adrenoceptor enhances platelet reactivity and might contribute to this phenomenon. For the present study, 121 stable angina patients on standard dual antiplatelet therapy (75 mg clopidogrel and 100 mg acetylsalicylic acid) were recruited. Born aggregometry was performed with adenosine diphosphate (ADP),collagen and epnephrine. To verify platelet adrenergic activity, potentiation by low-dose epinephrine and inhibition by selective alpha-2 receptor blocker atipamezole were determined. To assess the P2Y12-specific residual activity, cangrelor was used. Plasma norepinephrine, soluble CD40-ligand, high-sensitivity-C-reactive protein (hsCRP) - and in 24 subjects platelet P-selectin positivity were measured. Epinephrine - at very low concentration (10-9g/ml) - significantly potentiates (1.25 µM ADP: 26.5% vs. 43%; 5 µM ADP: 53% vs. 64.5%; collagen: 17% vs 42%, p<0.001) while atipamezole inhibits ADP- and collagen-induced platelet aggregations (1.25 µM ADP: 26.5% vs. 23%; 5 µM ADP: 53% vs. 47%;collagen:17% vs.11%,p<0.001).Patients with high adrenergic activity have significantly increased baseline ADP- and collagen-induced platelet aggregation. Based on cangrelor’s efficacy, these patients have significantly more residual P2Y12 activity as well.HsCRP and soluble CD40-ligand levels were similar.In conclusion, stable coronary heart disease patients with prominent adrenoceptor activity in vitro have significantly increased platelet aggregability and more functional P2Y12 receptor, indicating poor inhibitory response to thienopyridines.Therefore,platelet adrenergic receptor represents a considerable, dynamic factor of high residual platelet reactivity and might contribute to cardiovascular events indicating failure of antiplatelet therapy.
The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart
Authors: Lancel Steve , Decoster Brigitte , Asseman Philippe , Montaigne David , Marechal Xavier , Neviere Remi
Published: October 2008

Fondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo.However,the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown.To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.
Multiplexed genetic profiling of human blood platelets using fluorescent microspheres
Authors: Zhu Wei , Bahou Wadie F. , Gnatenko Dmitri V.
Published: October 2008

Human platelets have unique and reproducible mRNA profiles, with evidence for distinct profiles in haematopoietic stem cell disorders associated with thrombocytosis. Platelet transcript profiling is traditionally studied by microarray analysis, quantitative reverse transcription-PCR or serial analysis of gene ex-pression,techniques that are labor- and technically-intensive.We have now applied a novel multiplex-based platform for quantitative transcript profiling of human platelets.Simultaneous quantification of 17 platelet transcripts was assayed using intact platelet-rich plasma or gel-filtered platelets lysed in vitro.Accurate and reproducible profiles could be obtained from as few as 5 X 107 platelets (a platelet mass corresponding to ∼100 µl of whole blood), even for the low-abundant platelet transcripts. Correlation coefficients of this 17-member gene set to platelet Affymetrix microarrays were excellent (r2 = 0.949, p < 1 X 10–10), with no correlation to in kind-derived leukocyte profiles, highlighting the cell-specificity of the platform.These data demonstrate that transcript multiplexing using fluorescent micro-spheres can be adapted for rapid molecular profiling using intact platelets (bypassing the need for RNA isolation methods), with potential applicability irrespective of baseline platelet counts.
Treatment of acute pulmonary embolism as outpatients or following early discharge
Authors: Janjua Muhammad , Badshah Aaref , Matta Fadi , Danescu Liviu G. , Yaekoub Abdo Y. , Stein Paul D.
Published: October 2008

The purpose of this systematic review is to test the hypothesis that carefully selected low-risk patients with acute pulmonary embolism (PE) can safely be treated entirely as outpatients or after early hospital discharge.Included articles were required to describe inclusion or exclusion criteria and outcome of patients treated for PE.Early hospital discharge was defined as an average hospital stay ≤3 days.Six investigations included patients with PE who were treated entirely as outpatients; two investigations included patients with PE who were treated after early discharge. All investigations included only low-risk patients or patients with small or medium sized PE. Outcome after 3-46 months in patients treated entirely as outpatients showed recurrent PE in 0% to 6.2% of patients, major bleeding in 0% to 2.8% with one death from an intracerebral bleed. Definite death from PE did not occur, but there was one possible death from PE. Outcome in three months in patients treated after early discharge showed no instances of recurrent PE. Major bleeding occurred in 0% to 3.7% of patients.There were no deaths from PE, but there was one death from bleeding. In conclusion, outpatient therapy of acute PE is probably safe in low-risk,carefully selected compliant patients who have access to outpatient care if necessary. Such outpatient treatment would be cost-effective.
Characterization of calcium- and integrin-binding protein 1 (CIB1) knockout platelets: Potential compensation by CIB family members
Authors: Temple Brenda R. , Gentry Holly R. , DeNofrio Jan C. , Yuan Weiping , Parise Leslie V.
Published: October 2008

Platelet aggregation requires activation of the αIIbβ3 integrin,an event regulated by the integrin cytoplasmic tails. CIB1 binds to the cytoplasmic tail of the integrin αIIb subunit. Previous overexpression and knockdown studies in murine megakaryocytes demonstrated that CIB1 inhibits integrin αIIbβ3 activation.Here we analyzed Cib1-/-
mice to determine the function of CIB1 in platelets in vitro and in vivo. We found that although these mice had no overt platelet phenotype, mRNA level of CIB1 homolog CIB3 was increased in Cib1-/-
megakaryocytes. In vitro binding experiments showed that recombinant CIB1, -2 and -3 bound specifically to an αIIb cytoplasmic tail peptide. Subsequent protein modeling experiments indicated that CIBs 1–3 each have a highly conserved hydrophobic binding pocket. Therefore, the potential exists for compensation for the loss of CIB1 by these CIB family members, thereby preventing pathologic thrombus formation in Cib1-/-
mice.