bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas Embolism Caused by Portal Vein Gas: Case Report and Literature Review
Authors: Kamikado Chiaki , Nagano Shinjiro , Takumi Kouji , Senokuchi Terutoshi , Kubo Masaaki , Mitsue Shinji , Fukumoto Toshitaka , Natugoe Shouji , Aikou Takashi
Published: August 2008

Introduction: We describe a case of pulmonary gas embolism caused by portal vein gas (PVG) observed using echocardiography. Echography revealed gas flowing through the hepatic vein, inferior vena cava, right atrium, and right ventricle, as well as pulmonary hypertension. The patient was diagnosed as having pulmonary gas embolism caused by PVG. Objective: We consider PVG routes to pulmonary circulation, diagnosis of gas embolism caused by PVG, and treatment of gas embolism caused by PVG.Methods: We reviewed reports of eight cases of gas embolism caused by PVG and compared these cases to cases of gas embolism without PVG. Results: Mortality of gas embolism caused by PVG was 67%, positive blood culture was observed in six cases, and pulmonary edema was seen in three cases. PVG initially excites microbubble formation, which causes tissue damage in the liver and liver abscess. A large volume of PVG causes portal obstruction. As a result, portal hypertension, a portosystemic shunt or gastrointestinal congestion can occur. PVG can travel to the systemic vein through the liver or portosystemic shunt without anomaly and cause pulmonary gas embolism, followed by arterial embolism. In this environment, sepsis easily occurs. Echocardiography is useful for diagnosis of gas embolism caused by PVG, but the gas can be seen intermittently. The view of pulmonary edema is important for pulmonary gas embolism caused by PVG. Conclusion: It is important to treat the underlying disease, but PVG must be considered and treated as the gas embolism’s source.
Nonneural Congenital Abnormalities Concurring with Myelomeningocele: Report of 17 Cases and Review of Current Theories
Authors: Baradaran Nima , Ahmadi Hamed , Nejat Farideh , El Khashab Mostafa , Mahdavi Ali
Published: August 2008

Objective: Meningomyelocele (MMC) is a common central nervous system birth defect. Various congenital and acquired abnormalities have been reported with MMC, some of which are secondary to the pathophysiology and some are morbidities of the underlying disease. The aim of this study was to discuss current possible theories explaining diverse anomalies/abnormalities seen in a series of 390 patients with MMC. Methods: A retrospective study was performed using the records of 390 patients with MMC at Children’s Hospital Medical Center in Tehran, Iran, from January 2001 to January 2007. A series of 17 cases of MMC with attributed organ anomalies, not explained by a causal effect of the underlying disorder, were compiled. There were 3 cardiac anomalies including ventricular septal defect, pulmonary artery atresia and tetralogy of Fallot, 4 musculoskeletal malformations, consisting of missing rib, polydactylia and complex distal limb anomaly, 4 urological anomalies such as bladder exstrophy, horseshoe kidney and dysplastic kidneys, 2 occipital encephaloceles, 2 congenital adrenal hyperplasia patients with ambiguous genitalia, 1 omphalocele, 1 albinism and 1 Klippel-Feil syndrome. A review of the literature and discussion explaining each of these observations, have been performed and some possible theories have been proposed.Conclusions: Although various organ anomalies with different embryological origin had been observed and reported with MMC, it is difficult to explain their development using one of the current theories of MMC formation. It could be attributed to a possible genetic defect or merely an incidental finding. A teratological insult during the embryogenic phase would be an alternative assumption.
Intracranial Meningiomas in Children
Authors: Alexiou George A. , Mpairamidis Evriviadis , Psarros Antonios , Sfakianos George , Prodromou Neofytos
Published: August 2008

Background/Aims: Meningiomas, although common in adults, are rare in infancy and childhood. We present a single institution experience of children with meningiomas and a comparison of our findings with other published data. Methods: We reviewed the files of 352 children harboring a brain tumor, over a 16-year period. Eight cases of meningioma were verified (2.2%). All patients had been operated on and then had regular follow-up examinations. Results: There were 6 males and 2 females. The most common symptom was seizures. All tumors were intracranial and all patients underwent a gross total resection of the lesion. Six meningiomas were typical, whereas 2 patients had an atypical meningioma. After a mean 7-year follow-up period, all patients were in excellent condition, without evidence of tumor recurrence. Conclusion: Meningiomas, although rare, constitute a challenging problem. Gross total resection should be the goal and when it can be accomplished, the prognosis is excellent.
The Cerebral Arterial Circle (Circulus Arteriosus Cerebri)
Authors: Ardakani Shahab Kamali , Dadmehr Majid , Nejat Farideh , Ansari Saeed , Eftekhar Behzad , Tajik Parvin , El Khashab Mostafa , Yazdani Shahrooz , Ghodsi Mohammad , Mahjoub Fatemeh , Monajemzadeh Maryam , Nazparvar Bashir , Abdi-Rad Afshin
Published: August 2008

Background: Many studies have investigated the variations in the anatomy of each segment of the cerebral arterial circle while a few have addressed the variations of the cerebral arterial circle as a whole. Methods: Thirty brains of recently deceased Iranian infants and fetuses were dissected. The dissection process was filmed and digitized so as to be readily available for further studies. The variations of the circle as a whole and segmental variations were evaluated. Results: Variants with uni- and bilateral hypoplasia of posterior communicating arteries (PcoAs) were the most common in our study, similar to previous works. No aplasia of the precommunicating part of the anterior cerebral artery (A1), the precommunicating part of the posterior cerebral artery (P1) and anterior communicating artery was seen. Hypoplasia of the right and left PcoA was observed in 8 and 5 cases, respectively. Aplasia of the right PcoA was found in 16.6% and of the left PcoA in 3.3%. Conclusion: In this study, we confirmed the previously described finding that the symmetrical, circular configuration of the circulus arteriosus cerebri is present in only about 42.1%. The main differences between the fetal and adult disposition are the diameter of the PcoA and the circular part of the posterior cerebral artery. According to previous studies, the fetal brain older than 4 months has anatomical characteristics very similar to the adult’s circle; our finding was mostly similar to adult samples as most samples were from infants, not fetuses.
Use of Recombinant Human Bone Morphogenetic Protein-2 to Enhance Posterior Cervical Spine Fusion at 2 Years of Age: Technical Note
Authors: Oluigbo Chima O. , Solanki Guirish A.
Published: August 2008

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a genetically engineered protein which recruits bone-forming cells to the surgical area and converts local cells to bone. In clinical studies, rhBMP-2 successfully enhanced anterior/posterior spinal fusions in adult humans without bone grafts. Efficacy in paediatric spinal fusion is not yet reported. Methods: We describe the surgical technique and results in a 2-year-old girl with unstable C1–2 cervical spine injury who underwent non-metal-instrumented C1/C2 posterior spinal fusion using rhBMP-2 applied to an absorbable collagen sponge (ACS) matrix. Results: Radiologically verifiable bony fusion began at 3 weeks. Within 8 weeks solid C1-C2 spinal fusion was confirmed by CT scan. There was no evidence of spinal canal encroachment and no adverse effects related to the rhBMP-2/ACS-carrier matrix. Conclusion: rhBMP-2 enhanced posterior cervical fusion at an impressive rate in a very young child. This finding is encouraging both to effectiveness and speed. However, with all new developments, we highlight the need for further experience and longer follow-up in children.
Ruptured Middle Cerebral Artery Aneurysm in an Infant Presenting as Acute Subdural Hematoma: A Case Report
Authors: Adeleye Amos O. , Shoshan Yigal , Cohen Jose E. , Spektor Sergey
Published: August 2008

We present an unusual case of ruptured infantile cerebral aneurysm. An eight-month-old infant was delivered to the hospital in poor condition, after convulsions, with no history of trauma. His emergent CT study revealed acute subdural hematoma. The clinical and radiological picture evoked suspicion that the hematoma was of aneurysmal origin. The infant was operated with special preparations and precautions appropriate for aneurysmal surgery, and has shown a good recovery. It is important to consider the possibility of vascular accident in infants with subdural hematoma of nontraumatic origin. A good outcome may be achieved when appropriate preparations are made prior to surgery.
Craniovertebral Junction Anomaly with Atlas Assimilation and Reducible Atlantoaxial Dislocation: A Rare Constellation of Bony Abnormalities
Authors: Kumar Raj , Kalra Samir Kumar , Vaid Vivek Kumar , Sahu Rabi Narayan , Mahapatra Ashok Kumar
Published: August 2008

A rare case of craniovertebral junction anomaly with associated reducible C1-C2 dislocation and assimilation of the atlas is reported. The patient presented with neck pain with spastic quadriparesis. A posterior stabilization utilizing a contour rod, sublaminar wire fixation and onlay bone grafts between the occiput, and C3 and C4 vertebrae was performed followed by symptomatic improvement.
Rachipagus Parasite Associated with Myelocystocele and Diastematomyelia
Authors: Albert Gregory , Campos Mauricio , Menezes Arnold , Vogel Timothy , Weinstein Stuart
Published: August 2008

A case of parasitic rachipagus associated with myelocystocele, diastematomyelia and teratoma is presented. The parasite was successfully removed, and the spinal canal was reconstructed using bone harvested from the parasite.
Desmoplastic Infantile Ganglioglioma
Authors: Alexiou George A. , Stefanaki Kalliopi , Sfakianos George , Prodromou Neofytos
Published: August 2008

Desmoplastic infantile gangliogliomas (DIG) are rare intracranial tumors that typically occur in infants and involve the cerebral cortex and the leptomeninges. They are usually very large in size and partially cystic. Total resection, if possible, is the treatment of choice, without the need for further adjuvant therapy. We report 2 cases of DIG. In both cases, computed tomography and magnetic resonance imaging revealed supratentorial mixed cystic and solid tumors, which presented as large cystic components with intense contrast enhancement of a mural nodule. The tumors were completely removed by surgery. The histological diagnosis was DIG. On follow-up examinations no tumor recurrence was noted.
An Intracranial Pseudoaneurysm in the Distal Middle Cerebral Artery in a Child
Authors: Honda Masaru , Nagamine Tomoaki , Yamashiro Katsumi , Shimoji Takeyoshi
Published: August 2008

Intracranial pseudoaneurysms are rare, particularly in children and adolescents. They are characterized by the presence of organizing hematoma and fibrosis without true vascular elements. Most pseudoaneurysms result from events such as major trauma or infectious illness, and the development of pseudoaneurysm without a preceding incident is rare. We here describe a patient with a large pseudoaneurysm arising in the distal middle cerebral artery. A 10-year-old boy experienced a sudden onset of headache, nausea, and vomiting followed by loss of consciousness and was referred to our medical center. Brain computed tomography showed massive subcortical hemorrhage in the left temporal lobe. Digital cerebral angiography revealed a huge aneurysmal dilatation of the distal left M1 segment of the middle cerebral artery, with delayed filling and emptying of contrast media. Surgical resection of the aneurysm with evacuation of the hematoma yielded restoration of consciousness. Although the cause of aneurysm in this case is uncertain, this type of patient is seldom encountered; its etiology and mechanisms of onset are discussed with reference to the literature.
Lack of Association of Functional Variants in Alpha-ENaC Gene and Essential Hypertension in Two Ethnic Groups in China
Authors: Wang Xiao-feng , Lu Xiao-mei , Lin Ren-yong , Wang Shi-zhen , Zhang Li-ping , Qian Ji , Lu Da-ru , Wen Hao , Jin Li
Published: August 2008

Background: It has been proposed that subtle genetic changes in epithelial sodium channel (ENaC) subunits might be at the origin of less rare forms of hypertension. In some populations, subtle functional genetic changes in ENaC genes associated with essential hypertension were indeed observed. To further test this hypothesis, we observed the role of three functional variants G2139A, A334T and A663T in the alpha-ENaC gene on essential hypertension in two Chinese minority groups, the Kazaks and Uyghurs. Methods: A population-based case-control study was carried out in the two populations mentioned above. Results: The distribution of genotype and allele frequencies of G2139A, A334T and A663T did not differ significantly between hypertensive subjects and control subjects in both Kazak and Uyghur populations. No significant associations of the three polymorphisms with hypertension were observed in both populations in univariate and multivariate logistic regression analysis by applying dominant, additive and recessive models. Haplotype-based association analysis based on G2139A, A334T and A663T did not show significant association between hypertensive subjects and control subjects in both populations. Conclusions: For the above variants, we did not confirm the hypothesis that subtle genetic changes in alpha-ENaC subunits might be at the origin of essential hypertension in our populations.
Origin of Threshold Behaviour in Psoriatic Skin
Authors: Lejeune O. , Simonart T.
Published: August 2008

The mechanisms that lead to the psoriatic morphology are not fully elucidated. Several lines of evidence suggest that the positive feedback between keratinocytes and immunocytes plays a key role in the development of the lesions. On the other hand, little information is available on the negative regulatory controls that maintain a new homoeostasis level in psoriatic skin. We suggest here that the interplay of these two contrary feedbacks is likely to entail a hysteresis effect and that psoriasis is likely to be interpreted as a critical phenomenon characterized by a catastrophic shift of the skin from a normal to a hyperplastic state.
Treatment Following an Evidence-Based Algorithm versus Individualised Symptom-Oriented Treatment for Atopic Eczema
Authors: Schmitt Jochen , Meurer Michael , Schwanebeck Uta , Grählert Xina , Schäkel Knut
Published: August 2008

Background: Evidence-based treatment algorithms, successfully established for asthma, are missing for atopic eczema (AE). Objectives: To investigate whether treatment according to an evidence-based algorithm is an effective and applicable concept for the management of AE. Methods: Based on a systematic literature review, we developed an evidence-based severity-score-oriented treatment algorithm for AE and compared its effectiveness to that of an individualised symptom-oriented treatment (individual therapy) in a randomised controlled trial. Sixty-three participants were randomised to algorithm (n = 32) or individual therapy (n = 31) and treated accordingly for 12 months. Study end points included difference between baseline SCORAD and mean SCORAD under treatment (primary end point), quality of life and treatment utilisation. Analysis was by intention to treat (registration: ClinicalTrials.gov:NCT00148746). Results: No statistically significant differences in clinical or subjective response were observed between groups. Treatment following the algorithm and individual treatment both effectively controlled AE. Mean SCORAD reductions were 47% (95% confidence interval, CI = 38–55; algorithm) and 42% (95% CI = 29–54; individual). Clinical response was paralleled by improved quality of life in both groups. Physicians adhered to the algorithm option in 93% of their treatment decisions. Conclusion: Treatment following an evidence-based algorithm is an effective and applicable concept for the management of AE but does not show clear advantages compared to individualised treatment in a dermatological setting.
Ghosts of the Past II: Muscles and Fasciae in the Primate Forelimb Domain
Authors: Oxnard C.E. , Franklin D.
Published: August 2008

Many forelimb muscles (e.g. coracobrachialis, rhomboids, serratus sheet) are much less complex and much smaller in humans than in other primates. Yet human muscular variations and persistent fascial sheets indicate that increased size and complexity were once the norm. These muscular reductions are associated with equivalent skeletal gracilisation. Is it possible that molecular phenomena, not unlike those producing reduction of the jaw muscles and associated with gracilisation of the skull in species with reduced need for powerful mastication, may also have reduced forelimb muscles with gracilisation of its skeleton in species no longer using a forelimb for powerful locomotion? Could such molecular and skeletal changes be dated (as for the masticatory muscles) thus giving the time of origination of prehuman forelimb reduction and true bipedalism?
Serrated Adenoma of the Colorectum Undergoes a Proliferation versus Differentiation Process: New Conceptual Interpretation of Morphogenesis
Authors: Jiao Yu-Fei , Nakamura Shin-ichi , Sugai Tamotsu , Yamada Noriyuki , Habano Wataru
Published: August 2008

Objective: Serrated adenoma (SA) consists of glands both with intraluminal projection of tall columnar cells, which resemble the terminally differentiated cells in the surface epithelium, and with concave short cells, which resemble progenitor crypt cells of the colon. The aim of this study was to clarify the relationship between the serrated architecture and proliferation/differentiation process in SAs. Methods: The expressions of both terminally differentiated markers, such as p21, cytokeratin 20 and carbonic anhydrase I, and progenitor/proliferative markers, such as β-catenin, CD44 and Ki-67, were immunohistochemically examined in 43 SAs and 20 tubular adenomas. Results: P21-positive cells were more abundant in SAs than in tubular adenomas. Cytokeratin 20 and carbonic anhydrase I expressions were confined to the tall cells, while nuclear β-catenin and CD44 were expressed in the short cells in SAs. The Ki-67 labeling indices were significantly lower in tall cells than in short ones. Conclusions: SAs might undergo both proliferation and terminal differentiation, which is associated with unique serrated configuration.
Protein-Bound Polysaccharide K Partially Prevents Apoptosis of Circulating T Cells Induced by Anti-Cancer Drug S-1 in Patients with Gastric Cancer
Authors: Kono Koji , Kawaguchi Yoshihiko , Mizukami Yoshiki , Mimura Kousaku , Sugai Hidemitsu , Akaike Hidenori , Fujii Hideki
Published: August 2008

Background and Methods:It has been shown that T-cell dysfunction, including apoptosis of peripheral blood T cells, commonly occurs in patients receiving chemotherapy. In order to evaluate whether concomitant administration of the oral biological response modifier protein-bound polysaccharide K (PSK) could induce anti-apoptotic effects in patients treated with the anti-cancer drug, S-1, peripheral blood T cells were analyzed for induction of apoptosis, caspase-3 activities and expression of proapoptotic protein Bax and anti-apoptotic protein Bcl-2 in patients with curatively resected stage III gastric cancer, who were randomly assigned to postoperative adjuvant therapy with S-1 alone (n = 10) or S-1 combined with PSK (n = 10). Results: T-cell apoptosis 5 weeks after adjuvant therapy was significantly higher in the S-1 group (24.1 ± 5.0%) than in the S-1 + PSK group (19.1 ± 3.9%). S-1 induced T-cell apoptosis and concomitantly elevated caspase-3 activities and Bax expression in peripheral blood T cells. In addition, PSK partially prevented the T-cell apoptosis induced by S-1. Conclusion:PSK could partially prevent the T-cell apoptosis induced by S-1.
Targeting Her-2/neu in Breast Cancer: As Easy as This!
Authors: Azim Hamdy , Azim Jr. Hatem A.
Published: August 2008

Her-2/neu-positive tumors account for approximately 20% of all breast cancer and these tumors carry poor prognosis. Trastuzumab and lapatinib are 2 agents that have gained FDA approval for treating Her-2/neu-positive breast cancer. Trastuzumab has been shown to improve all endpoints when added to chemotherapy compared to chemotherapy alone, both in the adjuvant and metastatic phases. The addition of lapatinib to capecitabine has recently been shown to improve time to progression in trastuzumab-refractory patients with unique activity against brain metastasis. In spite of their impressive results, a significant fraction of patients still develop either primary or secondary resistance, a fact that entails the discussion of possible mechanisms of resistance. Biomarkers including PTEN, p95HER2, IGF1R and others have been linked to response to Her-2/neu-targeting agents. In this article, we overview the Her-2/neu signaling pathways and how a better understanding of the different molecular aspects of this oncogene could serve in optimizing the use of Her-2/neu-targeting agents. We also discuss the preclinical and clinical data of these biomarkers that may guide clinicians in choosing the right drug whenever possible.
Genetic Variation in Mouse Femoral Tissue-Level Mineral Content Underlies Differences in Whole Bone Mechanical Properties
Authors: Courtland Hayden-William , Spevak Mila , Boskey Adele L. , Jepsen Karl J.
Published: August 2008

A/J mice, as compared to C57BL/6J (B6) mice, have a significantly greater total femoral mineral (ash) content which correlates with an increased femoral stiffness (resistance to deformation), but also with an increased brittleness (catastrophic failure). To determine if this whole bone variation in mineral content is indicative of significant mineral and/or matrix variation at the tissue level, femora from 16-week-old female A/J and B6 mice were isolated, embedded in PMMA, sectioned and mounted on barium fluoride infrared windows for FTIRI analyses. In addition, preliminary studies of femora from C3H/HeJ (C3H) mice were conducted, since they have an ash content intermediate to A/J and B6. Mean values for mineral-to-matrix ratio were significantly different for A/J (8.4 ± 0.8) and B6 (7.5 ± 0.4), as were values for collagen cross-link maturity (1.8 ± 0.05 and 3.2 ± 0.1, respectively). C3H mice appeared to have a mineral-to-matrix ratio intermediate of A/J and B6, and cross-link maturity greater than both A/J and B6. B6 femora had similar carbonate-to-amide ratios, carbonate-to-mineral ratios and acid phosphate levels. Thus, whole bone differences in mineral content are concurrent with tissue-level variation in mineral content and collagen maturity in inbred mice. The greater stiffness and brittleness of A/J femora are likely due to differential biological control (osteoblast activity) of the amount of mineral.
Autophagy: A New Phase in the Maturation of Growth Plate Chondrocytes Is Regulated by HIF, mTOR and AMP Kinase
Authors: Srinivas Vickram , Bohensky Jolene , Shapiro Irving M.
Published: August 2008

The overall goal of the investigation was to examine autophagy in the growth plate and to ascertain how this process was regulated. Herein, we show that in the postmitotic maturing zone of the growth plate, chondrocytes express an autophagic phenotype. This robust and particulate immunohistochemical response provides direct evidence that autophagy is a new and transient stage in the chondrocyte maturation pathway. We found that induction of autophagy was regulated by mTOR, a sensor of cellular metabolism. When mTOR was inhibited, changes in LC3 fluorescence indicated that this kinase regulated development of the autophagic state. To determine if AMP kinase was required for chondrocyte autophagy, we suppressed its expression in N1511 cells using siRNA technology. When these cells were serum starved, a condition that triggers autophagy, there was no change in LC3 distribution. This result confirmed that AMP kinase was required for the induction of the autophagic response. Based on the 2 studies described above, and our previous observation that HIF-1 is required for the induction of autophagy, we put forward the hypothesis that autophagy is regulated by the activities of AMP kinase and mTOR in a HIF-1-dependent manner. Once autophagy is activated, the postmitotic chondrocytes would be expected to remain viable in their unique microenvironment and complete their life cycle.
Role of Phosphate Groups in Inhibition of Calcium Oxalate Crystal Growth by Osteopontin
Authors: Hunter Graeme K. , Grohe Bernd , Jeffrey Sara , O’Young Jason , Sørensen Esben S. , Goldberg Harvey A.
Published: August 2008

Osteopontin (OPN) inhibits the growth of calcium oxalate monohydrate (COM) and other crystal phases in a phosphorylation-dependent manner. In the present study, the role of OPN phosphate groups in adsorption to, incorporation into and inhibition of COM crystals was studied by comparing OPN isoforms differing in phosphorylation. OPN isoforms purified from rat bone (bOPN), which contains 10 phosphates, and cow milk (mOPN), which contains 25 phosphates, were compared with rat recombinant OPN (rOPN), which is not phosphorylated. Using fluorescence-labeled proteins and confocal microscopy, we show that mOPN and rOPN, like bOPN, adsorb preferentially to the edges between {100} and {121} faces of preformed COM crystals, and to a lesser extent to the {100} and {121} faces. Using scanning electron microscopy, we show that growth of COM in the presence of bOPN or mOPN results in a ‘dumbbell’ morphology, whereas crystals grown with rOPN are only slightly affected. COM crystals grown in the presence of low concentrations of fluorescence-labeled bOPN incorporate the protein into the crystal lattice. In crystals imaged in the {010} plane, incorporation of bOPN results in a cross-shaped pattern of fluorescence, consistent with preferential adsorption to {100}/{121} edges throughout the growth process.
Tissue Engineering Models of Human Digits: Effect of Periosteum on Growth Plate Cartilage Development
Authors: Landis William J. , Jacquet Robin , Lowder Elizabeth , Enjo Mitsuhiro , Wada Yoshitaka , Isogai Noritaka
Published: August 2008

Tissue-engineered middle phalanx constructs of human digits were investigated to determine whether periosteum wrapped partly about model midshafts mediated cartilage growth plate formation. Models were fabricated by suturing ends of polymer midshafts in a human middle phalanx shape with polymer sheets seeded with heterogeneous chondrocyte populations from bovine articular cartilage. Half of each midshaft length was wrapped with bovine periosteum. Constructs were cultured, implanted in nude mice for up to 20 weeks, harvested and treated histologically to assess morphology and cartilage proteoglycans. After 20 weeks of implantation, chondrocyte-seeded sheets adjacent to periosteum-wrapped midshaft halves established cartilage growth plates resembling normal tissue in vivo. Sheets adjacent to midshafts without periosteum had disorganized cells and no plate formation. Proteoglycans were present at both midshaft ends. Periosteum appears to guide chondrocytes toward growth plate cartilage organization and tissue engineering provides means for carefully examining construct development of this tissue.
Effects of VEGF on the Blood-Brain Barrier Disruption Caused by Hyperosmolarity
Authors: Chi Oak Z. , Hunter Christine , Liu Xia , Tan Tao , Weiss Harvey R.
Published: August 2008

This study was performed to test whether disruption of the blood-brain barrier (BBB) caused by hyperosmolarity could be related to vascular endothelial growth factor (VEGF), using anti-VEGF antibody and ciclopirox olamine (CPX), an inducer of VEGF. CPX 50 mg/kg or normal saline was given intraperitoneally to male Wistar rats 18 h before BBB disruption. Two craniotomies were made on the ipsilateral cortex (IC-1 and IC-2) where the BBB would be disrupted, and a third hole was made on the contralateral cortex (CC) to expose the cortices. We applied normal saline (to IC-1 and the CC) or anti-VEGF antibody (to IC-2) for 90 min before BBB disruption with intracarotid injection of 25% mannitol. The degree of BBB disruption was determined by measuring the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid and the volume of 3H-dextran distribution. The protein levels of VEGF were determined with Western blot analysis. In the control animals, hyperosmolar mannitol significantly increased (415%) the Ki in IC-1. The Ki was attenuated with anti-VEGF antibody application (–28%, p < 0.05). Even though the protein levels of VEGF were strongly increased with CPX pretreatment, this upregulation did not alter the hyperosmolar BBB disruption in the saline- or in the antibody-treated cortex. The data on the volume of dextran distribution followed the same pattern as that of the Ki but without a statistically significant difference between IC-1 and IC-2 in either group. Our data demonstrated that hyperosmolar BBB disruption could be attenuated with anti-VEGF antibody. However, upregulation of VEGF with CPX did not alter the degree of hyperosmolar BBB disruption with or without anti-VEGF antibody treatment. This study suggests that the contribution of VEGF in hyperosmolar BBB disruption is limited.
Formula-Based Estimates of the GFR: Equations Variable and Uncertain
Authors: Delanaye Pierre , Cohen Eric P.
Published: August 2008

Regarding the prevalence of chronic kidney disease in the population, estimation of glomerular filtration rate is of importance. Creatinine-based formulas are thus useful as the first step of a prevention strategy. Several creatinine-based formulas have been published. Among these, the Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD) study equation are the most used by physicians. The latter may be automatically reported by laboratories and has thus great success. However, these formulas have limitations. First, the MDRD formulas are not applicable to all populations, notably the healthy one and the patients with abnormal weight (anorectic or obese). Second, we evoke the limitations in the precision of the formulas linked to analytical aspects. Indeed, these analytical limitations remain significant even if they are improved by creatinine standardization. Lastly, we briefly mention the potential impact of these limitations on the epidemiology and the staging of chronic kidney disease.
Morphology of Glomerular Hematuria Is Reproduced in vitro by Carbonyl Stress
Authors: Degrell P. , Wagner Z. , Szijarto I.A. , Wagner L. , Marko L. , Mohas M. , Cseh J. , Wittmann I.
Published: August 2008

Abstract
Background: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be found in the urine; this is referred to as glomerular hematuria. Glomerulonephritides are characterized by increased carbonyl stress and elevated methylglyoxal (MGO) levels. MGO causes oxidative stress and intracellular calcium accumulation. In the present study, we investigated whether the effect of MGO-induced calcium accumulation in RBCs develops through increased oxidative stress. Furthermore, we studied whether MGO can lead to RBC membrane blebbing. Methods: RBC suspensions from healthy volunteers were incubated with different concentrations of MGO at 37°C. We measured oxidative stress and intracellular calcium level using fluorescent indicators. We determined the frequency of dysmorphic RBCs, and also performed scanning electron microscopy. Results: MGO increased oxidative stress and caused accumulation of calcium in isolated RBCs. These effects could be prevented using antioxidants. In the presence of MGO, RBC membrane blebbing developed. Conclusion: According to our findings, MGO causes calcium accumulation through oxidative stress. Carbonyl and oxidative stress may play an important role in the formation of dysmorphic RBCs in glomerular hematuria.
Bisphosphonate-Related Osteonecrosis of the Jaw: Model and Diagnosis with Cone Beam Computerized Tomography
Authors: Barragan-Adjemian C. , Lausten L. , Ang D.B. , Johnson M. , Katz J. , Bonewald L.F.
Published: August 2008

Intravenous bisphosphonate (BP) therapy has become the standard of care for the treatment of cancers that metastasize to bone. BPs are associated with osteonecrosis of alveolar bones, a condition known as osteonecrosis of the jaw (ONJ). The incidence or pathogenesis of ONJ is largely unknown. The lesions are characterized by areas of exposed necrotic bone that do not heal after 8 weeks in the absence of radiation to the head and neck. ONJ lesions have been recalcitrant to conventional therapies. Lesions in cancer patients treated with BPs develop in association with periodontal disease, tooth extraction and/or in association with increased mechanical force due to partial/complete dentures. We hypothesized that intravenous BPs in cancer patients impair normal bone remodeling, thereby increasing the incidence of osteonecrotic lesions and that these lesions can be detected using cone beam computerized tomography (CBCT). From CBCTs taken at the University of Missouri at Kansas City School of Dentistry, 26 subjects had a cancer diagnosis and were on BP therapy. From these 26 subjects, 18 presented visible, exposed necrotic bone. We observed both sclerotic and radiolucent lesions. Lesions could be detected and measured in reconstructed images where most were found to expand to large areas of the bone. We were able to identify necrotic bodies or ‘involucrums’ within the ONJ lesions, suggesting that this could be the mechanism for the formation of a clinically visible sequestrum. We propose that CBCT can potentially identify and follow the progression of both pre- and postclinical lesions in ONJ patients, allowing better diagnosis and assessment of disease status.
Exercise Alters Mineral and Matrix Composition in the Absence of Adding New Bone
Authors: Kohn David H. , Sahar Nadder D. , Wallace Joseph M. , Golcuk Kurtulus , Morris Michael D.
Published: August 2008

The mechanical properties of bone are dictated by its amount, distribution and ‘quality’. The composition of the mineral and matrix phases is integral to defining ‘bone quality’. Exercise can potentially increase resistance to fracture, yet the effects of exercise on skeletal fragility, and how alterations in fragility are modulated by the amount, distribution and composition of bone, are unknown. In this investigation, the effects of exercise on the size, composition, mechanical properties and damage resistance of bones from mice of various ages, background strains and genetic makeup were assessed, as a means of testing the hypothesis that mechanical loading can improve skeletal fragility via compositional alterations. C57BL/6 mice (4-month-old males) ran on a treadmill for 21 days. Tibiae from exercised and control mice were analyzed for cross-sectional geometry, mechanical properties, microdamage and composition. Exercise significantly increased strength without increasing cross-sectional properties, suggesting that mechanical stimulation led to changes in the bone matrix, and these changes led to the improvements in mechanical properties. Consistent with this interpretation, the mineral/matrix ratio was significantly increased in exercised bones. The number of fatigue-induced microcracks was significantly lower in exercised bones, providing evidence that exercise modulates fatigue resistance. The ratio of nonreducible/reducible cross-links mirrored the damage data. Similar trends (exercise induced increases in mechanical properties without increases in cross-sectional properties, but with compositional changes) were also observed in 2-month-old biglycan-deficient and wild-type mice bred on a C57BL/6x129 genetic background.
Mineral Deposition in the Extracellular Matrices of Vertebrate Tissues: Identification of Possible Apatite Nucleation Sites on Type I Collagen
Authors: Landis William J. , Silver Frederick H.
Published: August 2008

The possible means by which type I collagen may mediate mineralization in normal vertebrate bone, tendon, dentin and cementum as well as in pathological mineral formation are not fully understood. One consideration in this regard is that the structure of the protein is somehow important in binding calcium and phosphate ions in a stereochemical configuration conducive to nucleation of apatite crystals. In the present study, type I collagen, packed in a quarter-staggered arrangement in two dimensions and a quasi-hexagonal model of microfibrillar assembly in three dimensions, has been examined in terms of several of its charged amino acid residues. These included glutamic and aspartic acid, lysine, arginine, hydroxylysine and histidine, whose positions along the three α-chain axes of the collagen molecule were determined with respect to each other. It was found that the locations of these residues specified sites uniquely suited as potential apatite nucleation centers following binding of calcium and phosphate ions. From this analysis, it would appear that type I collagen provides a template of charged amino acid residues that dictates ion binding critical to subsequent nucleation events for mineral formation in vertebrate tissues.
Threshold Response of Initiation of Blood Coagulation by Tissue Factor in Patterned Microfluidic Capillaries Is Controlled by Shear Rate
Authors: Shen Feng , Kastrup Christian J. , Liu Ying , Ismagilov Rustem F.
Published: August 2008

Objective—

Blood flow is considered one of the important parameters that contribute to venous thrombosis. We quantitatively test the relationship between initiation of coagulation and shear rate and suggest a biophysical mechanism to understand this relationship.

Methods and Results—

Flowing human blood and plasma were exposed to cylindrical surfaces patterned with patches of tissue factor (TF) by using microfluidics. Initiation of coagulation of normal pooled plasma depended on shear rate, not volumetric flow rate or flow velocity, and coagulation initiated only at shear rates below a critical value. Initiation of coagulation of platelet-rich plasma and whole blood showed similar behavior. At constant shear rate, coagulation of plasma also showed a threshold response to the size of a patch of TF, consistent with our previous work in the absence of flow.

Conclusion—

Initiation of coagulation of flowing blood displays a threshold response to shear rate and to the size of a surface patch of TF. Combined with the results of others, these results set the range of shear rates that limit initiation of coagulation by small surface areas of TF and by shear activation of platelets. This range fits the relatively narrow range of physiological shear rates described by Murray’s law.
Dynamic of Hyperglycemia as a Predictor of Stroke Outcome in the ECASS-II Trial
Authors: Yong Mei , Kaste Markku
Published: August 2008

Background and Purpose—

Baseline hyperglycemia has been considered an independent predictor of stroke outcome. The present study analyzes the dynamics of serum glucose levels within the first 24 hours and its impact on stroke outcome.

Methods—

We studied 748 patients with acute ischemic hemispheric stroke in the second European Cooperative Acute Stroke Study (ECASS-II). The patients had 2 serum glucose measurements, at baseline and at 24 hours. Four dynamic patterns were defined as baseline hyperglycemia present only at baseline, 24-hour hyperglycemia present only at 24 hours, persistent hyperglycemia, ie, hyperglycemia at baseline and at 24 hours, and persistent normoglycemia, ie, normoglycemia at baseline and at 24 hours. The end points were 7-day neurological improvement on National Institutes of Health Stroke Scale, 30-day favorable functional outcome (Barthel Index 95 or 100), 90-day negligible dependence (modified Rankin Scale 0 to 2), all-cause mortality within 90 days, and hemorrhagic transformation on CT within the first 7 days.

Results—

In nondiabetic patients, persistent hyperglycemia was inversely associated with neurological improvement (OR=0.31; 95% CI=0.16 to 0.60), 30-day favorable functional outcome (OR=0.27; 95% CI=0.12 to 0.62), and 90-day negligible dependence (OR=0.36; 95% CI=0.17 to 0.73); it was associated with an increased risk of mortality within 90 days (OR=7.61; 95% CI=3.23 to 17.90) and for parenchymal hemorrhage (OR=6.64; 95% CI=2.63 to 16.78), whereas it was inversely associated with hemorrhagic infarction (OR=0.30; 95% CI=0.13 to 0.71). Delayed hyperglycemia at 24 hours was associated with the risks of death (OR=5.99; 95% CI=2.51 to 14.2) and parenchymal hemorrhage (OR=5.69; 95% CI-2.05 to 15.8) and inversely associated with no and negligible dependency (OR=0.40; 95% CI=0.20 to 0.78). Hyperglycemia at baseline only was not associated with any parameter of worse outcome. In patients with diabetes, the dynamic patterns of hyperglycemia did not suggest an association with stroke outcome.

Conclusions—

Persistent hyperglycemia was associated with all bad outcome end points studied. In addition to a single glucose measurement, the pattern of change should be considered in the prediction of stroke outcome.
Disparate Stroke Rates on Warfarin Among Contemporaneous Cohorts With Atrial Fibrillation
Authors: Hylek Elaine M. , Frison Lars , Henault Lori E. , Cupples Adrienne
Published: August 2008

Background and Purpose—

The rate of stroke among warfarin-treated patients in SPORTIF V was approximately half that of patients enrolled in SPORTIF III (1.16%/year versus 2.30%/year). SPORTIF III was an open-label trial comparing ximelagatran with warfarin for stroke prevention in atrial fibrillation. SPORTIF V was a double-blind trial performed in North America. The trial design was otherwise identical. We sought to determine if differences in baseline characteristics, use of potentially risk-modifying medications, or anticoagulation control help to explain the lower risk of stroke among warfarin-treated patients in SPORTIF V.

Methods—

Cox regression with stepwise model selection was used to define the covariates independently associated with stroke. Secondary analyses identified covariates with the strongest influence on the study factor (V/III). These covariates were then added to the primary model. Cox regression was used to determine the degree of confounding exerted by these covariates that might help to explain the differences between the trials.

Results—

Independent risk factors for stroke on warfarin included prior stroke/transient ischemic attack, coronary artery disease, international normalized ratio, weight, and study. Patients in SPORTIF V were at half the risk as those in SPORTIF III. We found that lower international normalized ratio variability, a higher proportion of prevalent warfarin use, lower systolic blood pressure, high-density lipoprotein, and a greater proportion of statin use among patients in SPORTIF V collectively conferred a lower risk of stroke.

Conclusion—

Differences in blood pressure control, international normalized ratio variability, proportion of prevalent warfarin users, statin exposure, and high-density lipoprotein collectively conferred a lower risk of stroke to patients in SPORTIF V. These findings suggest that the different event rates were not due to chance and provide potential insights into stroke risk among warfarin-treated patients with atrial fibrillation.
Are Rotations in Perceived Visual Vertical and Body Axis After Stroke Caused by the Same Mechanism?
Authors: Barra Julien , Benaim Charles , Chauvineau Valérie , Ohlmann Théophile , Gresty Michael , Pérennou Dominic
Published: August 2008

Background and Purpose—

The aim of this study was to investigate whether allocentric and egocentric coordinate systems are congruently biased after hemisphere stroke, which would suggest a single underlying mechanism.

Methods—

The perception of the long body axis (LBA), an egocentric reference, and that of the subjective visual vertical (SVV), an allocentric reference, was assessed in both the upright position and with 30° lateral body tilts in 15 patients with a hemisphere stroke and 12 control subjects.

Results—

In control subjects, estimates were accurate in upright but rotated in tilted positions (LBA 7°±6° overestimation and SVV 8.8°±7.8° toward the body). In patients, SVV (−4.4°±4.6°) and LBA (−4.8°±5.3°) were congruent in upright positions and when patients were ipsilesionally tilted (1.5°±7° and 1.9°±7°, respectively). In contrast, SVV and LBA were dissociated when the body was tilted to the contralesional side with overestimation of the LBA (−9.2°±4.6°) but no effect on SVV (−4.1°±6.4°).

Conclusions—

Because rotations in egocentric and allocentric reference systems found after stroke are differently modulated by lateral tilts, they are not due to a single underlying mechanism. However, they share common bases and can be simultaneously reduced by ipsilesional body tilt. Differences in the way somesthetic information is integrated may explain the differences in LBA and SVV.
CT Angiography-Source Image Hypoattenuation Predicts Clinical Outcome in Posterior Circulation Strokes Treated With Intra-Arterial Therapy
Authors: Schaefer Pamela W. , Yoo Albert J. , Bell Donnie , Barak Elizabeth R. , Romero Javier M. , Nogueira Raul G. , Lev Michael H. , Schwamm Lee H. , Gonzalez Ramon G. , Hirsch Joshua A.
Published: August 2008

Background and Purpose—

The aim of this study was to correlate CT angiography-source image (CTA-SI) parenchymal hypoattenuation with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis.

Methods—

In 16 patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis, we graded CTA-SI parenchymal hypoattenuation in the medulla, pons, midbrain, thalamus, cerebellum, occipital lobe, inferior parietal lobe, and medial temporal lobe. The grading scale was: 0, no hypoattenuation; 1, <50% hypoattenuation; and 2, >50% hypoattenuation. On CTA, we assessed clot location and length and collaterals. Outcome was measured with modified Rankin score.

Results—

Mean patient age was 68.3 years (range, 47 to 86 years), National Institutes of Health Stroke Scale was 28 (range, 11 to 40), time to CTA was 5.2 hours (range, 0.69 to 15.32), and time from CTA to intra-arterial thrombolysis was 5 hours (range, 2.25 to 10.38 hours). There were 4 basilar, 2 vertebral, and 10 combined occlusions. Eleven patients had near complete, 4 had partial, and one had no recanalization. Independent outcome predictors measured as modified Rankin score at 3 months were CTA-SI pons and midbrain scores(cumulative
r
=0.81,
P
<0.001). For outcome dichotomized into death versus survival, the CTA-SI pons score (
P
=0.0037) was the only independent predictor.

Conclusion—

Hypoattenuation in the pons and midbrain on pretreatment CTA-SI correlates highly with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis.