bluuebunny/crossref_metadata_2025 huggingface dataset:
Mastoid Cavity Dimensions and Shape: Method of Measurement and Virtual Fitting of Implantable Devices
Authors: Handzel Ophir , Wang Haobing , Fiering Jason , Borenstein Jeffrey T. , Mescher Mark J. , Leary Swan Erin E. , Murphy Brian A. , Chen Zhiqiang , Peppi Marcello , Sewell William F. , Kujawa Sharon G. , McKenna Michael J.
Published: April 2009

Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for three-dimensional reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira® software the area to be removed during such surgery is marked on axial CT slices, and a three-dimensional model of that space is created. The average volume of 31 reconstructed models is 12.6 cm3 with standard deviation of 3.69 cm3, ranging from 7.97 to 23.25 cm3. Critical distances were measured directly from the model and their averages were calculated: height 3.69 cm, depth 2.43 cm, length above the external auditory canal (EAC) 4.45 cm and length posterior to EAC 3.16 cm. These linear measurements did not correlate well with volume measurements. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurement unreliable. Hence, to assure successful implantation, preoperative assessment should include a virtual fitting of an implant into the intended storage space. The above-mentioned three-dimensional models were exported from Amira to a Solidworks application where virtual fitting was performed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications.
Cochlin-Tomoprotein: A Novel Perilymph-Specific Protein and a Potential Marker for the Diagnosis of Perilymphatic Fistula
Authors: Ikezono Tetsuo , Shindo Susumu , Sekiguchi Satomi , Hanprasertpong Charuk , Li Lishu , Pawankar Ruby , Morizane Toshio , Baba Shunkichi , Koizumi Yasuo , Sekine Kuwon , Watanabe Atsushi , Komatsuzaki Atsushi , Murakami Shingo , Kobayashi Toshimitsu , Miura Masakazu , Yagi Toshiaki
Published: April 2009

Background: Perilymphatic fistula (PLF) is an abnormal connection between the inner and middle ear. A procedure for obtaining definite proof of a PLF remains elusive, and methods of diagnosis remain controversial. To date, there is no clinically relevant biochemical marker for perilymph leakage. Using proteomic analysis of inner ear proteins, we have previously found unique properties of cochlin, encoded by the COCH gene. We detected 3 cochlin isoforms (p63s, p44s and p40s) in the inner ear tissue and a short 16-kDa isoform of cochlin-tomoprotein (CTP) in the perilymph. Since cochlin was found to be highly specific to the inner ear, we speculated that CTP might also be specific to the perilymph. The aim of this study was to determine whether CTP, a novel perilymph-specific protein, could be used as a marker for the diagnosis of PLF. Methods: By Western blotting, we investigated the specificity of CTP expression in a range of body fluids that included perilymph, serum, saliva and cerebrospinal fluid. To elucidate the detection limit of CTP, serially diluted recombinant human (rh)CTP as well as human perilymph was tested. Results: CTP was selectively expressed in all 20 perilymph samples tested, but not in 77 samples of the other body fluids. The detection limit of rhCTP was 0.27 ng or 0.022 μl of perilymph per well on Western blot analysis. Conclusion: The results strongly suggest that CTP can be a specific marker of perilymph leakage. Moreover, CTP has the potential to be a biochemical marker that allows a definitive diagnosis of the etiology of PLF-related hearing loss and vestibular disorders.
Induction of Tolerance by Oral Administration of Beta-Tubulin in an Animal Model of Autoimmune Inner Ear Disease
Authors: Cai Qing , Du Xiaoping , Zhou Bin , Cai Chun , Kermany Mohammad Habiby , Yoo Taijune
Published: April 2009

Induction of peripheral tolerance by oral administration of low-dose β-tubulin antigen may be an effective, antigen-specific method to suppress experimental autoimmune hearing loss. Five groups of mice were fed with phosphate-buffered saline (PBS), ovalbumin (OVA), 20, 30 or 200 μg of β-tubulin, respectively. All mice were then immunized by β-tubulin. Hearing thresholds were measured before and after immunization. Inner ear histology and cytokine profile were examined. Mice fed with 20 or 30 μg of β-tubulin showed less hearing loss and less inner ear damage compared to the groups treated with PBS, OVA or 200 μg of β-tubulin. Interferon-gamma (IFN-γ) was decreased while interleukin-4 (IL-4), IL-5, IL-13 and TGF-β were increased in both sera and in cell culture supernatants of the mice fed with 20 or 30 μg of β-tubulin. However, no cytokine profile change was found in the group treated with 200 μg of tubulin. These results suggest that a low dose of β-tubulin is active orally in an antigen-specific fashion and capable of inhibiting the autoimmune reactions in the inner ear by suppressingTh1 (IFN-γ) and increasing Th2 and Th3 (IL-4, IL-5, IL-13 and TGF-β) cytokines. Oral antigen tolerance may be used to treat autoimmune inner ear disease.
Exercise Intensity-Dependent Changes in the Inflammatory Response in Sedentary Women: Role of Neuroendocrine Parameters in the Neutrophil Phagocytic Process and the Pro-/Anti-Inflammatory Cytokine Balance
Authors: Giraldo E. , Garcia J.J. , Hinchado M.D. , Ortega E.
Published: April 2009

Background: It is still not really known what is the optimal level of exercise that improves, but does not impair or overstimulate the innate immune function. This is especially the case in women, who have higher basal levels of ‘inflammatory markers’ than men. The aim of this work was to evaluate differences in the magnitude of the stimulation of the innate/inflammatory response following a single bout of moderate or intense exercise in sedentary women, all of them in the follicular phase of their menstrual cycle. Changes in stress and sexual hormones were also evaluated. Methods: Changes induced by exercise (45 min at 55% VO2 max vs. 1 h at 70% VO2 max on a cycle ergometer) in the phagocytic process (chemotaxis, phagocytosis, and microbicide capacity against Candida albicans) and in serum concentrations of IL-1β, IL-2, IFN-γ, IL-12, IL-6, and IL-4 (ELISA) were evaluated. Parallel determinations were also made of serum or plasma concentrations of catecholamines (HPLC) and cortisol, oestradiol, and progesterone (electrochemiluminescence immunoassay). Results: Both exercise intensities increased chemotaxis, phagocytosis, and microbicide capacity of the neutrophils. However, the increase in chemotaxis was greater after moderate exercise. All the cytokines assayed were affected by exercise intensity. IFN-γ increased significantly only immediately after the intense exercise; IL-1β increased following both exercise intensities, although at 24 h it only remained elevated after the intense exercise; IL-12 only increased 24 h after the intense exercise, and IL-2 only showed a significant decrease following the moderate exercise. IL-6 increased immediately after both exercise intensities, but more so after moderate exercise. While IL-4 (an anti-inflammatory cytokine) increased following the moderate exercise, it decreased after the intense exercise. Both moderate and intense exercise increased norepinephrine and decreased cortisol, both of which returned to basal levels after 24 h. Only the intense exercise affected the epinephrine, oestradiol, and progesterone concentrations, with increases in epinephrine and oestradiol immediately after exercise, and a decrease in progesterone after 24 h. Conclusions: Both moderate and intense exercise stimulate the phagocytic process of neutrophils in sedentary women, but the profile of pro-/anti-inflammatory cytokine release seems to be better following the moderate exercise. The possible participation of stress (catecholamines and cortisol) and sex (oestradiol and progesterone) hormones in these intensity-dependent immune changes is discussed.
Linkage Effects and Analysis of Finite Sample Errors in the HapMap
Authors: Zaitlen Noah , Min Kang Hyun , Eskin Eleazar
Published: April 2009

The HapMap provides a valuable resource to help uncover genetic variants of important complex phenotypes such as disease risk and outcome. Using the HapMap we can infer the patterns of LD within different human populations. This is a critical step for determining which SNPs to genotype as part of a study, estimating study power, designing a follow-up study to identify the causal variants, ‘imputing’ untyped SNPs, and estimating recombination rates along the genome. Despite its tremendous importance, the HapMap suffers from the fundamental limitation that at most 60 unrelated individuals are available per population. We present an analytical framework for analyzing the implications of a finite sample HapMap. We present and justify simple approximations for deriving analytical estimates of important statistics such as the square of the correlation coefficient r2 between two SNPs. Finally, we use this framework to show that current HapMap based estimates of r2 and power have significant errors, and that tag sets highly overestimate their coverage. We show that a reasonable increase in the number of individuals, such as that proposed by the 1000 genomes project, greatly reduces the errors due to finite sample size for a large proportion of SNPs.
Linkage Analysis with Dense SNP Maps in Isolated Populations
Authors: Bellenguez Céline , Ober Carole , Bourgain Catherine
Published: April 2009

Objective: SNP maps are becoming the gold standard for genetic markers, even for linkage analyses. However, because of the density of SNPs on most high throughput platforms, the resulting significant linkage disequilibrium (LD) can bias classical nonparametric multipoint linkage analyses. This problem may be even stronger in population isolates where LD can extend over larger distances and with a more stochastic pattern. We investigate the issue of linkage analysis with SNPs from the Affymetrix 500K GeneChip array in extended families from the isolated Hutterite population. Methods: We minimized LD between SNPs by two methods based on a LD block pattern (Merlin and SNPLINK) and by MASEL, a new algorithm that we proposed to select SNP subsets with minimum LD and with no prior hypothesis about the LD pattern. Results: Simulations, performed using the real LD pattern observed in the Hutterite population, show that sizeable inflation of linkage statistics persist when LD between SNPs is minimized by Merlin and SNPLINK. Inflation of linkage statistics is better controlled with MASEL. Conclusion: In this population, it may be difficult to extract from standard GeneChip arrays a SNP map without LD-driven bias that is more informative than a dense microsatellite map.
Severe Brain Damage from Twin-Twin Transfusion Syndrome Treated with Serial Amnioreductions after 26 Weeks: A Case to Reconsider the Gestational Age Limits of Laser Therapy
Authors: Fichera A. , Ambrosi C. , Taddei F. , Gasparotti R. , Frusca T.
Published: April 2009

We report a case of monochorionic twin pregnancy complicated by twin-twin transfusion syndrome (TTTS) diagnosed in the late second trimester and treated with two amnioreductions. Three days after the first amniodrainage, the recipient twin developed intracranial ventriculomegaly and, similarly, after a few days, the donor showed signs of brain damage at MRI. We discuss the possible mechanism of brain damage of amnioreductions performed after 26 weeks of gestation in a monochorionic pregnancy with TTTS as a result of a placental ‘steal’ phenomenon.
Rationale and Design of a Randomized, Double-Blind, Parallel-Group Study of Terutroban 30 mg/day versus Aspirin 100 mg/day in Stroke Patients: The Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) Study
Authors: Bousser M.G. , Amarenco P. , Chamorro A. , Fisher M. , Ford I. , Fox K. , Hennerici M.G. , Mattle H.P. , Rothwell P.M. ,   on behalf of the PERFORM Study Investigators
Published: April 2009

Background: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. Methods and Results: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged ≥55 years, having suffered an ischemic stroke (≤3 months) or a transient ischemic attack (≤8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2–4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. Conclusions: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.
Endothelial Dysfunction in Lacunar Stroke: A Systematic Review
Authors: Knottnerus Iris L.H. , Ten Cate Hugo , Lodder Jan , Kessels Fons , van Oostenbrugge Robert J.
Published: April 2009

Background: Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients. Methods: We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunction in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and informative quality. The papers were categorized into subheadings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium. Results: 29 articles were eligible for further analysis. We found 16 publications on regulation of vascular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilatation and CO2 reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular endothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion molecules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers. Conclusions: The current literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endothelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well-defined cases and combine multiple methods to evaluate endothelial function.
Comparison of EXIT-25 and the Frontal Assessment Battery for Evaluation of Executive Dysfunction in Patients Attending a Memory Clinic
Authors: Moorhouse Paige , Gorman Mary , Rockwood Kenneth
Published: April 2009

Background/Aims: The Frontal Assessment Battery (FAB) and the EXIT-25 have emerged as 2 widely used screening instruments for executive dysfunction, but their screening properties have not been evaluated in a head-to-head comparison. Methods: Prospective cohort study of 92 individuals presenting for cognitive assessment at a community hospital. Results: The EXIT-25 took longer than the FAB to complete (mean difference = 9.27 min, 95% CI: 9.86–8.68). EXIT-25 and FAB scores showed significant correlation (Spearman’s r = –0.79, p < 0.001) with one another, and each showed acceptable convergent validity and divergent validity. Conclusions: The 2 tests provide similar information about the presence of executive dysfunction. The FAB takes less time to complete, and appears to be less frustrating for patients, making it more feasible as a screening test for executive dysfunction in a memory clinic setting.
Towards a Novel Vaccine against Human Cytomegalovirus Based on a Chimeric Ad5F35 Adenovirus Vector Expressing the Immunodominant Antigenic Domain 1 Epitope
Authors: Zhao Ping , Ma Daoxin , Yan Shuxin , Shao Na , Zhang Jingru , Bi Zheng , Dai Jianjian , Ji Min , Ji Chunyan
Published: April 2009

Background: Antibodies induced from glycoprotein B (gB) by antigenic domain (AD)-1 demonstrate broad neutralizing activity across different human cytomegalovirus (HCMV) types. This study aimed to prepare a novel HCMV vaccine using the modified adenoviral vector Ad5F35 to direct the expression of the conserved HCMV epitope AD-1 and to determine its transfer and expression in peripheral blood mononuclear cells (PBMCs). Methods: AD-1 genes were amplified from AD169 HCMV strain and cloned into the Ad5F35 vector. Ad5F35-AD-1 virus vaccine was prepared by packaging Ad5F35-AD-1 into HEK293 cells. RT-PCR and fluorescence detection were used to detect the expression of AD-1 in HEK293 cells. PBMCs were stimulated in vitro with Ad5F35-AD-1 virus vaccine. The AD-1 expression in PBMCs was determined with immunocytochemistry and cell viability was measured to observe the possible adverse effects of AD-1 on PBMCs. Results: We constructed an Ad5F35-AD-1 vector and transferred it into HEK293 cells to prepare the Ad5F35-AD-1 virus vaccine successfully. The AD-1 gene was proved to be expressed in HEK293 cells. In vitro stimulation of PBMCs with Ad5F35-AD-1 showed the highly efficient expression of AD-1 and low cytopathic activity in PBMCs. Conclusion: The novel vaccine Ad5F35-AD-1 is a promising candidate for clinical trials and may be of utility in prime-boost strategies for HCMV prevention and control.
Sunitinib Malate, a Receptor Tyrosine Kinase Inhibitor, Is Effective in the Treatment of Restrictive Heart Failure due to Heart Metastases from Renal Cell Carcinoma
Authors: Szmit Sebastian , Zagrodzka Magdalena , Kurzyna Marcin , Opolski Grzegorz , Szczylik Cezary
Published: April 2009

Few systematic trials have studied metastatic tumors to the heart and there are currently no guidelines for the treatment of heart metastases and its associated symptoms. This article presents the first known case of effective pharmacological treatment of heart failure due to metastases of renal cell carcinoma (RCC). Due to pressure caused by metastatic tissue on the left atrium and the decreased blood inflow to the left ventricle, the 61-year-old male patient suffered from dyspnea. Treatment with sunitinib, an oral multitargeted receptor tyrosine kinase inhibitor, was initiated and led to a decrease in the mass of the metastasis infiltrating the left atrium. Arterial hypertension caused by sunitinib therapy was effectively controlled by the use of an angiotensin-converting-enzyme inhibitor. Therapy with sunitinib reduced the symptoms of exercise intolerance; the patient felt much better and was able to return to his family and resume professional activity. Further studies are required to confirm the utility of sunitinib therapy in patients with symptoms of heart failure due to heart metastases from RCC.
Rapid Clinical Assessment of Patients with Acute Heart Failure: First Blood Pressure and Oxygen Saturation – Is That All We Need?
Authors: Milo-Cotter Olga , Cotter Gad , Kaluski Edo , Rund Michele M. , Felker G. Michael , Adams Kirkwood F. , O’Connor Christopher M. , Weatherley Beth Davison
Published: April 2009

The risk stratification of patients with acute heart failure (AHF) has been addressed repeatedly in recent years. Low oxygen saturation (SaO2) and systolic blood pressure (SBP) are signs of impending respiratory and circulatory failure that can be obtained quickly in patients with AHF. Methods: Admissions for AHF (340 patients) in a city hospital were recorded and patients were followed for symptoms of heart failure, re-admission and mortality for 6 months. Results: Patients with low (<90%) SaO2 had higher rates of worsening heart failure at 1 month and 6 months (p < 0.001 and p < 0.001, respectively) and higher rates of mortality (p = 0.013). SBP <120 mm Hg was not associated with a significant increase in worsening heart failure, but was associated with a statistically significant increase in mortality at 1 and 6 months (p < 0.001 and p < 0.001, respectively). Combined low SaO2 and SBP had a particularly strong prognostic implication. Patients who developed frank respiratory failure and/or circulatory failure fared the worst. Patients requiring ventilatory support had a recurrent heart failure rate of 81% and a mortality of 41% at 1 month of follow-up. Patients requiring intravenous pressors without respiratory mechanical support had a recurrent heart failure rate of 72% and a mortality rate of 28% at 1 month (p < 0.001). Conclusions: Simple assessment of impending respiratory and circulatory failure at admission by measuring SaO2 and SBP enables rapid and accurate risk stratification of patients admitted for AHF. This may enable more aggressive therapeutic interventions for stabilization and treatment of AHF.
Extreme Polycythemia in Recipient Twin with Twin-to-Twin Transfusion Syndrome: A Case Report
Authors: Braig Ute , Henrich Wolfgang , Dudenhausen Joachim W. , Obladen Michael , Czernik Christoph
Published: April 2009

We report a case of severe polycythemia in the recipient twin of a pregnancy with twin-to-twin transfusion syndrome (TTTS). Stage I TTTS was suspected at initial presentation (24 weeks) due to discordant growth associated with a twin oligo-polyhydramnios sequence. Increasing peak systolic velocity (PSV) in the middle cerebral artery (MCA) of the donor twin indicated fetal anemia. In addition, we observed a decreasing MCA-PSV of the recipient twin, indicating polyglobulia. Close follow-up without intervention showed a stable course of TTTS without progression to higher stages.Following caesarean section at 31 2/7 weeks due to preterm premature rupture of membranes of the leading donor twin, the donor twin showed anemia (hematocrit 28%) whereas the recipient twin demonstrated severe polycythemia (hematocrit 88%). Inter-twin difference of reticulocyte counts was high (38% for the donor and 5% for the recipient twin). Transfusion and partial exchange transfusion (PET) were performed in the donor and in the recipient twin, respectively. Normal hematocrit levels were achieved without complication. Perinatal outcome of both twins was good. Conclusion: Even in a stable course of pregnancy with stage I TTTS, severe polycythemia of the recipient twin can occur and can require careful PET in a specialized center.
Healthcare Expenditure and Resource Utilization in Patients with Anaemia and Chronic Kidney Disease: A Retrospective Claims Database Analysis
Authors: Wish Jay , Schulman Kathy , Law Amy , Nassar George
Published: April 2009

Background/Aims: We conducted a retrospective claims database analysis to examine the association of anaemia and anaemia management with healthcare expenditure and utilization in patients with chronic kidney disease (CKD) before the onset of dialysis. Methods: Claims data on patients (aged ≥15 years) with CKD were collected from the Medstat Marketscan® Commercial and Medicare Databases between 2000 and 2005. Using these data, patients were evaluated for anaemia of CKD, anaemia treatment status and healthcare costs and use. Results: Of the 37,105 CKD patients, 9,807 (26%) had incident anaemia; 59% of these received at least one type of anaemia treatment, with 48% receiving an erythropoiesis-stimulating agent. The total adjusted per patient per month healthcare expenditure for all CKD patients was USD 2,749. Patients with anaemia had significantly greater overall expenditure, which was 38% higher than those without anaemia. Total expenditure was 17% higher for untreated versus treated anaemic patients, largely due to higher inpatient expenditure in the untreated cohort. Conclusion: This analysis suggests that the presence of anaemia is associated with greater medical expenditure in patients with CKD. However, we found that anaemia management may help to lower inpatient costs associated with anaemia in the CKD population.
Infections Related to Airway Stenting: A Systematic Review
Authors: Agrafiotis Michalis , Siempos Ilias I. , Falagas Matthew E.
Published: April 2009

Background: Airway stenting is nowadays an established method for the palliative and/or curative treatment of central airways obstruction. However, complications related to the use of airway stents have been reported. Objective: We endeavored to systematically evaluate the currently available evidence regarding the infections associated with airway stenting. Methods: We independently searched in PubMed for relevant reports. We considered articles which reported on clinical infections related to airway stenting. A case was identified as stent-associated respiratory tract infection (SARTI) according to the authors of the individual papers, based on clinical findings with or without radiological or microbiological confirmation. Results: Twenty-three articles (19 cohorts/case series and 4 case reports), involving 501 patients with airway stents, were included. The indication for airway stenting was malignancy and benign disease in 45 and 55% of the included patients, respectively. Ninety-three (19%) out of the 501 stented patients experienced SARTI. Pneumonia was the most common type of SARTI (47%), followed by bronchial infection (24%), cavitary pneumonia/lung abscess and intraluminal fungus ball. Staphylococcus aureus (39%) and Pseudomonas aeruginosa (28%) were the most commonly identified pathogens. Twenty-six (68%) out of the 38 patients with SARTI, for whom outcome data were available, died. Conclusion: The accumulated and evaluated evidence suggests that SARTI probably involves 1 in 5 patients with airway stent. Although the possibility of SARTI should not discourage the interventional pneumologists from inserting airway stents, the data seem to underline the urgent need for establishing a consensus definition and diagnostic criteria for SARTI.
Sarcoidosis and Melanoma: A Referral Center Study of 1,199 Cases
Authors: Seve Pascal , Schott Anne Marie , Pavic Michel , Broussolle Christiane , Gilis Lila , Thomas Luc
Published: April 2009

Background: Case reports and small short case series have described patients with sarcoidosis and melanoma. Objectives: To examine the relation between sarcoidosis and melanoma. Methods: Computerized search of all patients seen at our department of dermatology between 1998 and 2007 and review of the literature using a Medline search from 1985 to June 2008. Results: We identified 7 cases in our population of 1,199 melanoma inpatients. Including these cases, 20 cases of sarcoidosis have been described in melanoma patients. Fifteen patients had their sarcoidosis diagnosed after melanoma. In 7 cases, sarcoidosis was related to immunotherapy. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. Conclusion: Our referral center study shows a prevalence of sarcoidosis of 0.58% among melanoma inpatients. Clinicians should be aware of the possibility that sarcoidosis may initially manifest itself in melanoma patients, especially after treatment with immunotherapy, and mimic metastatic disease.
Regeneration of a Spinal Ligament after Total Lumbar Disk Arthroplasty in Primates
Authors: Cunningham Bryan W. , Berven Sigurd H. , Hu Nianbin , Beatson Helen J. , De Deyne Patrick G. , McAfee Paul C.
Published: April 2009

Total disk arthroplasty (TDA) is a new procedure that replaces the intervertebral disk space with an artificial motion segment and necessitates the resection of the anterior longitudinal ligament (ALL). We assessed whether a collagen-based graft made from porcine small-intestine submucosa (SIS) can be used as a regenerative scaffold to restore the function and structure of the ALL in the lumbar spine. A total of 10 mature male baboons underwent TDA at L5–L6 using one of two treatments: (1) TDA only (n = 5) or (2) TDA combined with SIS (n = 5). Six months postoperatively, mock revision surgery was performed to assess tissue adhesions followed by non-destructive multidirectional flexibility testing of the spinal segment. The vertebral segments were then processed for histology. The tissue adhesion score was 2.8 ± 0.8 in the TDA only group and 1.8 ± 1.4 in the TDA-SIS group (p = 0.2). Segmental range of motion and the length of the neutral zone were similar in both groups. Histology showed that the SIS scaffold led to an organized ligamentous structure with a significantly (p = 0.027) higher thickness (2.18 ± 0.25 mm) compared to the connective tissue structure in the TDA-only group (1.66 ± 0.33 mm). We concluded that using a SIS bioscaffold after TDA did not lead to increased great vessel adhesion while its use facilitated the formation of highly organized ligamentous tissues. However, the SIS- induced and newly formed ligamentous tissue anterior to the spinal segment did not lead to a measurable limitation of spinal extension.
Purification of Blood Coagulation Factors II, VII, IX and X from Bovine Citrated Plasma
Authors: Reekers P. , Hemker H.C.
Published: April 2009

The bovine coagulation factors II, VII, IX and X were separated from other plasma proteins, and each factor was obtained in a largely pure state by various chromatographic procedures in the presence of diisopropylfluorophosphate (DFP). Factor X was separated from factors II, VII, and IX by DEAE Sephadex chromatography, followed by G-100 filtration and hydroxylapatite chromatography. Separation of factors II and IX from factor VII was achieved by chromatography on DEAE cellulose, followed by G-100 gel filtration and hydroxylapatite chromatography. Factors II and IX were separated by preparative polyacrylamide electrophoresis. After DEAE cellulose chromatography, factor VII was purified by gradient elution from hydroxylapatite.
Thrombin Clotting Time – a More Sensitive Indicator of Denatured Fibrinogen than Clottability
Authors: Ly B. , Godal H.C. , Kierulf P.
Published: April 2009

Following moderate denaturation of purified fibrinogen by heat or alkali, the thrombin time was more seriously affected than was clottability. Clottability was unaffected by time moderate heat denaturation, denoting that retained clottability after various preparative procedures does not necessarily rule out conformational changes in the fibrinogen molecule. During the action of thrombin upon denatured fibrinogen, enhanced generation of N-terminal glycine was demonstrated, reflecting increased susceptibility to thrombin. This is in accordance with the increased susceptibility of denatured proteins to proteolytic enzymes generally found. Since visible gelation was delayed in denatured fibrinogen, this means that the native conformation of fibrinogen is not essential for the proteolytic action of thrombin, but is essential for the subsequent polymerisation of the fibrin formed.
Hobby-Induced Factor VII Deficiency
Authors: Pinkhas J. , Cohen I. , Kruglak J. , de Vries A.
Published: April 2009

Hemorrhagíc tendency and granulocytopenia due to prolonged contact with trichloroethylene and toluene are described in a boy whose hobby was model air-plane assembly. The hemostatic defects found were hypoproconvertinemia, moderate hypofibrinogenemia, and increased capillary fragility. The clinical and laboratory abnormalities disappeared following interruption of the exposure. The abnormalities in the coagulation mechanism are ascribed to a toxic effect of the trichloroethylene on the liver, while the granulocytopenia is considered to reflect a bone marrow-depressing action of benzene contaminating the toluene. The increased capillary fragility is presumed to be due to a toxic effect of the chemicals on the blood vessels.
Platelet Aggregation and Populations in Acute Leukaemias
Authors: Caen J. , Rendu Francine , Sultan Yvette , Gruyer P. , Scrobohaci Marie-Lorraine , Levy-Toledano Sylviane , Delobel J. , Flandrin G. , Bernard J.
Published: April 2009

We have tried to correlate abnormal functions of platelets – mainly aggregation – with the cellular type of acute leukaemia. In acute lymphoblastic leukaemia, the abnormalities of platelet aggregation – when found – are related to plasmatic abnormalities. In acute monoblastic leukaemia, the platelet aggregation with ADP and the release are abnormal and the occurrence of a megacaryocytopathy is suggested. The results found in five cases of acute myeloblastic leukaemia – all peroxydase-positive – were heterogenous; three of the patients were abnormal, mainly with an abnormal release, while two – one of whom being pseudolymphoblastic – were normal when tested before or during effective therapy. These results can be helpful in the understanding of the marrow involvment in different types of acute leukaemia.
Hyperactive Connective Tissue in Seven Patients with Recurrent Thrombotic Occlusions
Authors: Hedner Ulla , Nilsson Inga Marie , Bergentz S.-E. , Cronberg L.
Published: April 2009

A saline extract from the fascia of musculus rectus abdominis with increased capacity to aggregate the platelets in vitro was found in two uraemic patients with recurrent obstructive thrombosis frequently complicating the shunts used for haemodialysis, and in five patients with recurrent spontaneous deep venous thrombosis. None of these patients had any other disorder known to predispose to thrombosis. The increased capacity of the fascia extract to induce platelet aggregation may be due to a hitherto unknown cause of thrombosis, namely a defect in the collagen structure or in the subendothelial substances.
Variation of the Proelastase/Elastase Ratio in Human Blood Platelet Populations
Authors: Legrand Y. , Pignaud G. , Fauvel F. , Caen J.
Published: April 2009

Human blood platelets have been separated into four populations according to their density, and the elastase activity measured in the presence and absence of trypsin in each of the four populations. Trypsin dependent elastolytic activity (proelastase) was higher in heavy (C and D) than in light (A and B) platelets, whereas trypsin independent elastolytic activity (elastase) was higher in light than in heavy platelets. The proelastase is presumably activated into fully active elastase as the platelet becomes lighter by an endogenous activating system.
Effects of Some Polyene Antibiotics on Human Platelets and their Function
Authors: van der Plas P.M. , Kraan L. , Stibbe J. , Hemker H.C.
Published: April 2009

(1) Polyenes aggregate platelets. The aggregation power diminishes in the following order: filipin > nystatin > etruscomycin∼pimaricin. (2) In the case of filipin, aggregation is probably caused by damage to platelets resulting in a release of platelet contents, which subsequent aggregates the remaining platelets. (3) Filipin-induced aggregation can be partially inhibited by adenosine and is Ca++-dependent. (4) Collagen- and ADP-induced aggregation can be inhibited by low concentrations of etruscomycin. (5) Polyenes are able to release platelet factor 3 from thrombocytes. The strength decreases in the following order: filipin > nystatin > etruscomycin > pimaricin. (6) The uptake of serotonin by platelets is diminshed by polyenes. Leakage of 86Rb from preloaded platelets increases upon addition of polyenes.
Different Cross-Over Electrophoretic Mobility of Factor Friuli X and Coumarin-induced Abnormal Factor X
Authors: Girolami A. , Bareggi G. , Fioretti D.
Published: April 2009

Lyophilized or frozen plasmas with congenital deficiencies of factors II, VII, IX, or X, abnormal factor X (factor X Friuli) plasma, absorbed normal plasma, plasmas from patients treated with coumarin anticoagulants and normal plasma were studied in a crossover electrophoresis (electrosyneresis) system using an anti-factor X antiserum. A factor X band was present in plasmas with a deficiency of factors II, VII, and IX, in abnormal factor X plasma, and in normal plasma. No difference in the position of the factor X band was noted for all these plasmas. In coumarin plasma, two factor X bands were evident. The first of these two bands had the same position as the normal factor X band; the second one migrated slightly more towards the cathode. In adsorbed normal plasma and in factor X deficient plasma, no bands were seen. Minor, lighter bands were seen in most plasmas on the cathodic side of the slide and thought to represent secondary activities of the antiserum. These results suggest that the abnormal factor X (factor X Friuli) has the same crossover electrophoretic mobility as normal factor X, whereas the coumarin-induced abnormal factor X has a different mobility.
Differential Interaction of Clotting Factors II, VII, IX and X with Sephadex and Dextran Blue
Authors: Swart A.C.W. , Kop-Klaassen B.H.M. , Hemker H.C.
Published: April 2009

A preparation of coagulation factors II, VII, IX, and X was obtained by adsorption onto Al (OH)3 from normal plasma. The subsequent eluate was subjected to gel filtration experiments. It was noticed that the purification obtained on Sephadex G-100 columns was hardly dependent upon the characteristics of the buffer. Factor VII is partly separated from the other factors. Factors II and IX appear to be of equal size, whereas factor X is slightly larger. Molecular weights of about 72,000–74,000 were calculated for factors II, IX, and X, and 57,000–59,000 for factor VII. The coagulation factors are bound to dextran blue, depending upon the ionic strength. Factors II and IX are much more tightly bound than factors VII and X. At an ionic strength of 0.15 and pH 7.0, both, factor II and factor IX interact strongly with dextran blue, whereas the other factors remain free. On the basis of this effect, nearly complete separation can be achieved. The interaction between the factors and dextran blue decreases with increasing pH.
Factor VIII Inhibitor in a Patient with Mild Hemophilia A
Authors: Lechner K. , Ludwig E. , Niessner H. , Thaler E.
Published: April 2009

A weak inhibitor of factor VIII (0.75 U/ml) appeared in a 20-year-old patient with mild hemophilia A (factor VIII 6 %) during therapy with cryoprecipitate. The inhibitor had a biological half-life time of 6 days. After a period in which neither inhibitor nor factor VIII were detectable, factor VIII activity reappeared 81 days after beginning of treatment.
Phosphoribosylpyrophosphate Synthetase and Purine Phosphoribosyltransferases in Human and Rabbit Blood Platelets
Authors: Jerushalmy Z. , Sperling O. , Pinkhas J. , Krynska M. , de Vries A.
Published: April 2009

Phosphoribosylpyrophosphate synthetase and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activities were demonstrated in human and rabbit platelet lysates. Comparative measurement of HGPRT activity and adenine phosphoribosyltransferase activity showed the latter to be higher than the former in human platelet lysates and the reverse in rabbit platelet lysates.
Effect of Prostaglandin E1, on Experimental Thrombosis and Platelet Aggregation in Rabbits
Authors: Bousser Marie-Germaine , Lecrubier Chantal
Published: April 2009

Prostaglandin E1 (PGE1) was found to be a powerful inhibitor of platelet thrombus formation in injured rabbit-brain arteries, the inhibiting effect being immediate, constant, proportional to the infusion rate, powerful, but tran- sient. PGE1 inhibited platelet aggregation induced by ADP, collagen, and a mixture of ADP-adrenaline in blood samples taken during PGE1 infusions into rabbits, the inhibitory effect also being immediate and transient, but moderate, variable, and not strictly proportional to the dose. This discrepancy suggests that PGE1 acts by affecting not only circulating platelets but also the arterial wall; it stresses again that experimental thrombosis as well as in vitro tests should be used in assessing potentially antithrombotic agents.
The Molecular Components and Fibrinolytic Activity of Human Thrombin
Authors: Mills Donald A. , Karpatkin Simon
Published: April 2009

Purified human thrombin was electrophoresed on SDS-gel. A single major band of approximately 38,000 mol. wt. was obtained. After reduction of disulfide bonds a chain of 33,000 mol. wt. was found, suggesting release of a 5,000 mol. wt. sulfhydryl-attached peptide. The purified human thrombin slowly lysed fibrin in a manner different from that of plasmin and in addition to the release of peptides A and B. This activity may be responsible for some of the apparent heterogeneity of fibrinogen in vivo.
Interaction of Early Fibrinogen Degradation Products with Soluble Fibrin
Authors: Ly B. , Jakobsen E.
Published: April 2009

Purified fibrinogen was exposed to a limited action of thrombin, further thrombin activity being prevented by hirudin. Agarose gel chromatography of the soluble material revealed formation of derivatives of higher molecular weight than that of the parent fibrinogen molecule. When 125I-fibrinogen was added just before chromatography, a great proportion of the radioactivity was eluted together with the high molecular weight derivatives (HMWD), indicating copolymerization of fibrin monomer and fibrinogen. In contrast, 125I-FDP, consisting mainly of fragments X and Y, were only to a small extent eluted with HMWD, suggesting that early FDP are less capable of linking with fibrin monomer, than is fibrinogen. The ability of early FDP to link with fibrin was markedly increased, however, upon treatment with thrombin. Thus, early FDP copolymerize with fibrin monomer provided that fibrinopeptide A, known to be retained, is released.
Interrelations between the Clotting and Kinin Systems
Authors: Stormorken Helge , Gjoennaess Halvard , Laake Knut
Published: April 2009

A survey is given of the most recent work on interrelations between the coagulation and kinin systems. The recent identification of the Fletcher factor with prekallikrein has established another link between the clotting and kinin systems besides factor XII. Further links are provided by the cold activation of factor VII by factor XII-prekallikrein, and the feedback activation of factor XII by kallikrein. These new apprehensions also have consequences for the theory of intrinsic clotting, and the relation between the intrinsic and extrinsic system, and emphasize the complex function of factor XII.
Anticoagulant-Antithrombin and Fibrinolytic Actions of Extract of Marine Alga Corallina Rubens L
Authors: Güven K.C. , Ulutin Ş.B. , Mutluay E. , Ulutin O.N.
Published: April 2009

The extract of Corallina rubensL. and its fractions were studied chemically, and their effects on the coagulation and fibrinolytic systems were investigated.Thin-layer and paper chromatographic studies of these fractions showed a polypeptide structure. One of them (fraction I) contains a sugar component consisting of 7 different monosaccharides. Antithrombin activity The extract of C. rubens and its fractions were examined in regard to their actions on coagulation and fibrinolysis. The anticoagulant-antithrombin effect of fraction I was found to be more powerful than that of the extract and of fraction III. Fraction I also had an inhibitory effect on fibrinolysis. The sum of these activities in the total extract of C. rubens was an activator action on fibrinolysis with an anticoagulant-antithrombin effect. The fibrinolysis-activating effects were found in fraction II and fraction III.
Complex Formation between Fibrinogen, Fibrinogen Degradation Products and Insolubilized Fibrin Monomer at Various pH Values
Authors: Matthias F.R.
Published: April 2009

In order to gain insight into the complex formation occurring among fibrinogen and its derivatives under conditions of a disturbed acid-base balance in streptokinase therapy, experiments were carried out in which the adsorption of fibrinogen and its degradation products X, Y, D, and E was assessed on insolubilized fibrin monomer at pH 6.0 and 7.8. Products X and Y were tested in isolated form; the end products of lysis, D and E, were purified but not separated. The fragments were adsorbed in a higher yield at pH 7.8, whereas fibrinogen combined to a higher extent at pH 6.0. The possible consequences of this phenomenon are discussed.
Influence of Prostaglandin E1 on Platelet Decrease in the Heart-Lung Machine
Authors: Stibbe J. , Ong G.L. , ten Hoor F. , Nauta J. , van der Plas P.M. , Vergroesen A.J. , de Jong D. , Krenning-Douma E.
Published: April 2009

It was investigated whether the decrease of platelet count, which occurs during open heart surgery with the use of the heart-lung machine (HLM), is a result of platelet adhesion and/or aggregation. PGE1 in concentrations of 100, 10 and 5 ng/ml, respectively, inhibited platelet decrease in human heparinized blood circulating in the HLM in vitro. It is concluded that under the conditions used the adhesion/aggregation process is involved and that platelet aggregates are circulating. The relation to platelet function, organ impairment by micro-embolization and the function of filters in the HLM in cardiopulmonary bypass are discussed.
Induction of Aggregation and of the Release Reaction in Human Platelets by Polylysine
Authors: Massini P. , Metcalf L.C. , Näf U. , Lüscher E.F.
Published: April 2009

Polylysine aggregates human blood platelets and, within a concentration range which is typical for a given preparation, can elicit the release reaction. No evidence for a relation between the active concentration range of different polylysine preparations and their structure or molecular weight could be established. ADP stimulates the release at ub- or superoptimal concentrations of polylysine. These results support the hypothesis that cell contact, here facilitated by the polycation, ADP, fibrinogen and calcium ions are required for the induction of the release reaction. Once these components are available in adequate amounts within a polylysine-induced aggregate, the release reaction will be propagated automatically throughout the aggregate.
Hemostatic Defects in Experimental Leukemia
Authors: Rasche H. , Hoelzer D. , Dietrich M. , Keller A.
Published: April 2009

Hemostatic defects in rats of the inbred strain BDIX suffering from transplanted acute leukemia (L 5222) are described. Prolongations of the clotting time, reduction of thrombus solidity, decrease in peripheral platelet counts and factor XIII activity, as well as defects in the extrinsic and intrinsic pathway of coagulation indicate occurrence of a hemorrhagic tendency in the course of the disease. On the other hand, there is a significant increase of fibrinogen and antithrombin III. The value of the animal model as a useful tool in investigating yet unsolved hemostatic problems in human acute leukemia is discussed.