bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased cerebral glucose metabolism in patients with brain tumors: an effect of corticosteroids
Authors: Fulham Michael J. , Brunetti Arturo , Aloj Luigi , Raman Ramesh , Dwyer Andrew J. , Di Chiro Giovanni
Published: June 2009

✓ The authors measured cerebral glucose metabolism (CMRglu) using [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in patients with brain tumors to evaluate the effect of exogenous corticosteroids (in this instance, dexamethasone) on glucose metabolism. Fifty-six FDG-PET studies obtained in 45 patients with unilateral supratentorial brain tumors were analyzed. Patients with brain tumors were divided into three groups: 1) patients with cushingoid symptoms, who had been treated with combinations of radiotherapy and chemotherapy taking oral dexamethasone; 2) patients not taking dexamethasone but treated with radiotherapy; and 3) patients not taking dexamethasone who had not been treated with radiotherapy. Serial FDG-PET scans were obtained in eight of the cushingoid patients. Glucose metabolism was measured in the contralateral cerebral and ipsilateral cerebellar hemispheres in patients and compared to measurements taken from 19 normal volunteers. The authors found that in the cushingoid brain tumor patients there was a marked reduction in CMRglucompared to normal volunteers and other brain tumor patients (Kruskal—Wallis test; p 0.001). In the majority of patients who had serial FDG-PET scans, there was a decline in glucose metabolism over time and in one patient, in whom dexamethasone was reduced in dosage, there was a subsequent increase in CMRglu. The authors conclude that there is a generalized reduction in CMRgluin brain tumor patients taking dexamethasone compared to other brain tumor patients and normal volunteers, and that this effect is independent of radiotherapy, concurrent anticonvulsant medication, and transhemispheric functional disconnection (transhemispheric diaschisis).
Inhibition by 5′-methylthioadenosine of cell growth and tyrosine kinase activity stimulated by fibroblast growth factor receptor in human gliomas
Authors: Miyaji Katsuya , Tani Eiichi , Nakano Atsuhisa , Ikemoto Hideyasu , Kaba Keizo
Published: June 2009

✓ Stimulation of three human glioma cell lines with basic fibroblast growth factor (bFGF) led to the enhancement of cell growth and the rapid tyrosine phosphorylation of cellular proteins, including major substrates of 90 kD. A methyltransferase inhibitor, 5′-methylthioadenosine (MTA), inhibited dose dependently the bFGF-stimulated cell growth and protein tyrosine phosphorylation in glioma cells by blocking both receptor autophosphorylation and substrate phosphorylation, as shown by immunoblotting with antiphosphotyrosine antibodies and cross-linking bFGF to receptors. The antiproliferative activity of MTA correlated quantitatively with its potency as an inhibitor of bFGF-stimulated protein tyrosine kinase activity. The methyltransferase inhibitor MTA had no effect on either epidermal growth factor— or platelet-derived growth factor—stimulated protein tyrosine phosphorylation in glioma cells, but inhibited specifically bFGF-stimulated protein tyrosine kinase activity. The concentration of MTA required for inhibition of protein methylation correlated well with the concentration required for inhibition of bFGF-stimulated cell growth and protein tyrosine phosphorylation. Because MTA had no effect on numbers and dissociation constants of high- and low-affinity bFGF receptors, the inhibition of bFGF-stimulated bFGF receptor tyrosine kinase activity is not likely to be the result of a reduction in bFGF receptor and bFGF binding capacity. In fact, MTA delayed and reduced the internalization and nuclear translocation of bFGF, and the internalized bFGF was submitted to a limited proteolysis that converted it to lower molecular peptides whose presence remained for at least 22 hours. The effect of MTA on bFGF-stimulated tyrosine phosphorylation was immediate and readily reversible.
Primary diffuse leptomeningeal oligodendroglioma
Authors: Chen Robert , Macdonald David R. , Ramsay David A.
Published: June 2009

✓ The authors describe a case of a diffuse primary leptomeningeal oligodendroglioma in a 17-year-old girl who presented with raised intracranial pressure and hydrocephalus. She underwent imaging studies and a left frontotemporal craniotomy that revealed a cystic oligodendroglioma in the suprasellar cistern and spread of neoplastic cells to the spinal leptomeninges. The tumor showed little response to maximum radiotherapy and chemotherapy, and the patient died from complications of high-dose chemotherapy 2 years after diagnosis. Postmortem examination of the brain and spinal cord revealed diffuse meningeal infiltration by neoplastic cells and no evidence of an intraparenchymal origin. Glial heterotopias were noted at several sites along the brain base, adding circumstantial support to the theory that leptomeningeal gliomas are derived from ectopic glial tissue in the subarachnoid space.
Bobble—head doll syndrome and drop attacks in a child with a cystic choroid plexus papilloma of the third ventricle
Authors: Pollack Ian F. , Schor Nina F. , Martinez A. Julio , Towbin Richard
Published: June 2009

✓ The authors report an unusual case of a 2-year-old boy with a 3-month history of episodic rightward anterolateral head tilt and large-amplitude positional anteroposterior head bobbing reminiscent of bobble—head doll syndrome. This child experienced a sudden onset of drop attacks and then, within several hours, deep coma. The causative lesion was a contrast-enhancing, partially cystic third ventricular mass, which ultimately obstructed the aqueduct, producing profound obstructive hydrocephalus. An emergency ventriculostomy and endoscopic fenestration of the septum pellucidum was performed. Four days later, the tumor was completely resected by a transcallosal—transforaminal approach. The lesion was freely mobile within the third ventricle and contained a large cyst within its posterior pole; following drainage of the cyst, the lesion was easily delivered through the foramen of Monro. The histopathological diagnosis was choroid plexus papilloma.

The child's neurological deficits, head tilt, and head bobbing resolved immediately after operation. To the best of the authors' knowledge, this represents the first well-documented report of bobble—head doll syndrome and drop attacks secondary to a choroid plexus papilloma. The highly mobile nature of the cystic lesion presumably led to its intermittent impaction within the foramen of Monro and/or proximal aqueduct; this produced the intermittent head tilt and bobble-head symptoms and, ultimately, resulted in acute obstruction of the aqueduct, causing the child's precipitous neurological decline.
Frontal plagiocephaly secondary to synostosis of the frontosphenoidal suture
Authors: Francel Paul C. , Park T. S. , Marsh Jeffrey L. , Kaufman Bruce A.
Published: June 2009

✓ Frontal plagiocephaly may arise from either synostotic or deformational forces. Deformational causes of frontal plagiocephaly can be distinguished from synostotic causes by differences seen on physical examination, which can then be confirmed by skull x-ray films and if necessary three-dimensional computerized tomography (CT). Unilateral coronal synostosis is the main synostotic cause of frontal plagiocephaly, although it has also been seen with fusion of the frontozygomatic suture. In several syndromes presenting with bilateral coronal synostosis, fusion of the frontosphenoidal and frontoethmoidal sutures is also present.

The authors report, for perhaps the first time, a case showing synostotic frontal plagiocephaly secondary to fusion of the frontosphenoidal suture alone. Although the phenotypic appearance is superficially similar to that seen in unilateral coronal synostosis, analysis of the cranial base shows markedly different effects: angulation of the anterior cranial base with respect to the posterior cranial base away from the synostotic side and angulation of the posterior cranial base with respect to the midpalatal suture also away from the synostotic side. In unilateral coronal synostosis, both angulations are toward the synostotic side. These effects on the cranial base alter its relationship to the cranial vault and the facial skeleton. Most important, frontal plagiocephaly secondary to fusion of the frontosphenoidal suture should not be overlooked as being deformational. Because this fusion is difficult or impossible to visualize by skull x-ray films, three dimensional CT must be obtained in cases that are not clearly identified as deformational plagiocephaly by physical examination.
Preservation of the arteries around an aneurysm: practical use of oxycellulose
Authors: Kodama Namio , Matsumoto Masato , Sasaki Tatsuya
Published: June 2009

✓ The authors describe an intraoperative technique, in which oxycellulose is placed between an aneurysm and its surrounding arteries, allowing a space to be secured for inserting the clip blades without occlusion of the arteries. This method is useful in preserving the blood vessels, especially perforating arteries, around the aneurysm.
Responding to change: the challenge of the 1990s
Authors: Seljeskog Edward L.
Published: June 2009

✓ In 1995, neurosurgery in the United States is facing challenges and threats never before imagined. In its attempts to respond as a relatively small specialty, the neurosurgical community can no longer afford to remain a house divided. Neurosurgical unity has now become a critical matter. In particular, our neurosurgical leadership must minimize duplication of efforts and efficiently allocate its resources. Most importantly, it must unify its energies in directing the numerous joint American Association of Neurological Surgeons/Congress of Neurological Surgeons activities, as well as serving as a direct liaison with the emerging representative assembly under the Joint Council of State Neurosurgical Societies. The unification of the neurosurgical leadership will clearly enhance our ability to deal with all of our present challenges and future changes, but more importantly it will permit our specialty to truly speak with one voice.
Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations
Authors: Kondziolka Douglas , Lunsford L. Dade , Flickinger John C. , Kestle John R. W.
Published: June 2009

✓ The benefits of radiosurgery for cavernous malformations are difficult to assess because of the unclear natural history of this vascular lesion, the inability to image malformation vessels, and the lack of an imaging technique that defines “cure.” The authors selected for radiosurgery 47 patients who harbored a hemorrhagic malformation in a critical intraparenchymal location remote from a pial or ependymal surface. Of these, 44 patients had experienced at least two hemorrhages before radiosurgery. The mean patient age was 39 years; six patients had previously undergone attempted surgical removal. The malformation was located in the pons/midbrain in 24 cases, the medulla in three, the thalamus in nine, the basal ganglia in three, deep in a parietal lobe in four, and deep in a temporal lobe in four. Patients had sustained initial hemorrhages from 0.5 to 12 years prior to radiosurgery (mean 4.12 years). In these patients, who were not typical of the majority of patients with cavernous malformations, there were 109 bleeds before radiosurgery in 193 prior observation-years, for a 56.5% annual hemorrhage rate (including the first hemorrhage), or an annual rate of 32% subsequent to the first hemorrhage.

The mean follow-up period after radiosurgery was 3.6 years (range 0.33–6.4 years). The proportion of patients with hemorrhage after radiosurgery was significantly reduced (p < 0.0001), as was the mean number of hemorrhages per patient (p = 0.00004). In the first 2 years after radiosurgery, there were seven bleeds in 80 observation-years (8.8% annual hemorrhage rate). In the 2- to 6-year interval after radiosurgery, the annual rate decreased to 1.1% (one bleed). After radiosurgery, 12 patients (26%) sustained neurological worsening that correlated with imaging changes. In eight patients these deficits were temporary; two underwent surgical resection and died. Two patients had new permanent deficits (4%). A significant reduction was observed in the hemorrhage rate after radiosurgery in patients who had deep hemorrhagic cavernous malformations, especially after a 2-year latency interval. This evidence provides further support to the belief that radiosurgery is an effective strategy for cavernous malformations, especially when located within the parenchyma of the brainstem or diencephalon.
Functional changes in cultured strips of canine cerebral arteries after prolonged exposure to oxyhemoglobin
Authors: Yoshimoto Yuhei , Kim Phyo , Sasaki Tomio , Kirino Takaaki , Takakura Kintomo
Published: June 2009

✓ The present study was undertaken to determine whether oxyhemoglobin (OxyHb) is responsible for the functional alterations in the cerebral arteries observed during chronic vasospasm after subarachnoid hemorrhage. Vascular strips of canine basilar arteries were kept in organ culture for 3 days with or without repetitive exposure to OxyHb (OxyHb-treated and control strips). Contractions elicited by high levels of potassium (80 mM) and uridine 5′-triphosphate (3 × 10−4M) were reduced in the OxyHb-treated group in a concentration-dependent manner. The relaxations evoked by nitric oxide and 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) were not affected. Relaxations elicited by the calcium channel blocker, diltiazem, were attenuated in the OxyHb-treated rings. When the extracellular calcium concentration ([Ca++]e) was changed from a concentration in the external solution of 10−8M to 10−3M, myogenic tension developed. Myogenic tension, expressed as a percentage of the maximum contraction in each segment, was augmented in the OxyHb-treated group at [Ca++]eof 10−5M and 10−4M. There were no significant differences in passive compliance of the arterial wall between the two groups. These results demonstrated that prolonged exposure to OxyHbin vitroresults in a decrease in contractile capacity and an increase in sensitivity to [Ca++]e, in agreement with previous findings in spastic arteries. By contrast, impairment of the 8-bromo-cGMP—mediated relaxation pathway and increased stiffness of the arterial wall, which have been reported to occur in spastic arteries, were not induced by prolonged exposure to OxyHbin vitro.
Chronic postinjury administration of MDL 26,479 (Suritozole), a negative modulator at the GABAA receptor, and cognitive impairment in rats following traumatic brain injury
Authors: O'Dell Dianne M. , Hamm Robert J.
Published: June 2009

✓ The present experiment examined the efficacy of postinjury administration of MDL 26,479 (Suritozole), a negative modulator at the γ-aminobutyric acidA (GABAA) receptor that enhances cholinergic function, in attenuating spatial memory deficits after traumatic brain injury in the rat. Two experiments were performed. In the delayed-dosing experiment, rats received a moderate level (2.1 atm) of fluid-percussion brain injury and were tested in the Morris water maze 11 to 15 days following injury. These rats were injected with either 5 mg/kg (eight rats) or 10 mg/kg (eight rats) of MDL 26,479 60 minutes before each water maze test. Additional rats were injured and treated with saline (eight rats) or were surgically prepared but not injured (eight rats). In the second experiment, an early postinjury dosing procedure was followed. Rats were injured in the same manner but drug treatment began 24 hours after injury and continued daily through Day 15. Results indicated that the rats in the delayed chronic dosing regimen did not differ from the injured, saline-treated rats in their latency to reach the goal platform (p > 0.05). However, those treated chronically beginning 24 hours after injury had significantly shorter latencies than the injured, saline-treated rats (p < 0.05). These results suggest that administration of agents that enhance cholinergic function may be an appropriate strategy for promoting cognitive recovery when given after traumatic brain injury. Furthermore, prolonged treatment may be necessary to elicit beneficial effects.
Expression of bcl-2 in reactive and neoplastic astrocytes: lack of correlation with presence or degree of malignancy
Authors: Krishna Murli , Smith Thomas W. , Recht Lawrence D.
Published: June 2009

✓ The bcl-2 protooncogene encodes a 26-kD protein that extends cell survival by blocking apoptosis. This protein has been found to be overexpressed in neoplastic neural cell lines, although its expression in reactive and neoplastic astrocytes in vivo has not been well characterized. The authors hypothesized that bcl-2 oncoprotein expression in gliomas might be positively correlated with the tumor's degree of malignancy. Sixty-three gliomas of various subtypes and histological grades were immunostained by bcl-2 protein and the percentage of positive cells was quantitatively assessed. All tumors contained neoplastic cells that were immunoreactive for the bcl-2 protein (range of cell positivity 1%–53%). It was found that bcl-2 expression did not vary significantly as a function of tumor subtype or grade (p < 0.1, one-way analysis of variance (ANOVA) on ranks) as compared to the cell proliferation marker Ki-67 (MIB-1) in which a very significant correlation with tumor grade was noted (p < 0.0000001, one-way ANOVA on ranks). In fact, the highest percentage of bcl-2 immunoreactive cells was noted in low-grade gliomas, that is, in juvenile pilocytic astrocytomas and oligoastrocytomas. The specificity of bcl-2 overexpression was also assessed in 10 nonneoplastic lesions associated with prominent reactive astrocytosis. In nine of these cases (90%), bcl-2—positive reactive astrocytes were observed, often in large numbers, whereas relatively few Ki-67 immunoreactive cells were noted. The authors conclude that bcl-2 oncoprotein expression as assessed immunohistochemically does not correlate with glial tumor type or grade and its overexpression is not confined only to neoplastic conditions. Instead, the finding of robust bcl-2 expression in low-grade glial tumors and in reactive astrocytes warrants the inference that resistance to apoptosis is a nonspecific finding in astrocytes associated with both reactive and neoplastic conditions.
Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy
Authors: Siegal Tali , Horowitz Aviva , Gabizon Alberto
Published: June 2009

✓ Anthracyclines entrapped in small-sized, sterically stabilized liposomes have the advantage of long circulation time, reduced systemic toxicity, increased uptake into systemic tumors, and gradual release of their payload. To date, there is no information on the behavior of these liposomes in brain tumors. The objective of this study was to compare the biodistribution and clinical efficacy of free doxorubicin (F-DOX) and stealth liposome—encapsulated DOX (SL-DOX) in a secondary brain tumor model. Nine days after tumor inoculation Fischer rats with a right parietal malignant sarcoma received an intravenous dose of 6 mg/kg of either F-DOX or SL-DOX for evaluation of drug biodistribution. For therapeutic trials a single dose of 8 mg/kg was given 6 or 11 days after tumor induction, or alternatively, weekly doses (5 mg/kg) were given on Days 6,13, and 20. Liposome—encapsulated DOX was slowly cleared from plasma with a t1/2 of 35 hours. Free-DOX maximum tumor drug levels reached a mean value of 0.8 µg/g and were identical in the adjacent brain and contralateral hemisphere. In contrast, SL-DOX tumor levels were 14-fold higher at their peak levels at 48 hours, declining to ninefold increased levels at 120 hours. A gradual increase in drug levels in the brain adjacent to tumor was noted between 72 and 120 hours (up to 4 µg/g). High-performance liquid chromatography analysis identified a small amount of aglycone metabolites within the tumor mass from 96 hours and beyond, after SL-DOX injection. Cerebrospinal fluid levels were barely detectable in tumor-bearing rats treated with F-DOX up to 120 hours after drug injection (≥ 0.05 µg/ml), whereas the levels found after SL-DOX were 10- to 30-fold higher. An F-DOX single-dose treatment given 6 days after tumor inoculation increased the rats' life span (ILS) by 135% over controls (p < 0.05) but was not effective if given on Day 11. In contrast, SL-DOX treatment resulted in an ILS of 168% (p< 0.0003) with no difference when given after 6 or 11 days. Treatment with three weekly doses of SL-DOX produced an ILS of 189% compared to 126% by F-DOX (p < 0.0002). The authors conclude that the use of long-circulating liposomes as cytotoxic drug carriers in brain tumor results in enhanced drug exposure and improved therapeutic activity, with equal effectiveness against early small- and large-sized brain tumors.
Prolonged survival of mice with glioma injected intracerebrally with double cytokine—secreting cells
Authors: Lichtor Terry , Glick Roberta P. , Kim Tae Sung , Hand Roger , Cohen Edward P.
Published: June 2009

✓ A novel approach toward the treatment of glioma was developed in a murine model. The genes for both interleukin-2 (IL-2) and interferon-γ (IFN-γ) were first transfected into a mouse fibroblast cell line that expresses defined major histocompatibility complex (MHC) determinants (H—2k). The double cytokine—secreting cells were then cotransplanted intracerebrally with the Gl261 murine glioma cell line into syngeneic C57BL/6 mice (H—2b) whose cells differed at the MHC from the cellular immunogen. The results indicate that the survival of mice with glioma injected with the cytokine-secreting allogeneic cells was significantly prolonged, relative to the survival of mice receiving equivalent numbers of glioma cells alone. Using a standard51Cr-release assay, the specific release of isotope from labeled Gl261 cells coincubated with spleen cells from mice injected intracerebrally with the glioma cells and the cytokine-secreting fibroblasts was significantly higher than the release of isotope from glioma cells coincubated with spleen cells from nonimmunized mice. The cellular antiglioma response was mediated by natural killer/lymphokine-activated killer and Lyt-2.2+(CD8+) cells. The increased survival of mice with glioma and the specific immunocytotoxic responses after immunization with fibroblasts modified to secrete both IL-2 and IFN-γ indicate the potential of an immunotherapeutic approach to gliomas with cytokine-secreting cells.
Huge Langerhans cell histiocytosis granuloma of choroid plexus in a child with Hand-Schüller-Christian disease
Authors: Kim Eun-Young , Choi Joong-Uhn , Kim Tai-Seung , Kim Dong-Ik , Kim Kir-Young
Published: June 2009

✓ In the literature, only two previous cases of presumed Langerhans cell histiocytosis (LCH) granuloma involving choroid plexus have been reported in patients with Hand-Schüller-Christian (HSC) disease, but those cases were not verified by immunohistochemistry or electron microscopy. The authors report a case of LCH granuloma of the choroid plexuses of bilateral lateral ventricles and the fourth ventricle in a child affected by HSC disease. This disease was confirmed by the presence of Birbeck granules on electron microscopy and positive reactivity to S-100 protein. Clinical, radiographic, and histological features are discussed. This case illustrates that LCH granuloma should be considered in the differential diagnosis of intraventricular masses.
Gradual resolution of an arachnoid cyst after spontaneous rupture into the subdural space
Authors: Rakier Anatoly , Feinsod Moshe
Published: June 2009

✓ The authors present the case of a young patient in whom the spontaneous rupture of a known, long-standing middle fossa arachnoid cyst into the subdural space was documented. This spontaneous rupture was followed by gradual diminution of the cyst to near-complete resolution.
Safe removal of retained ventricular catheters using intraluminal choroid plexus coagulation
Authors: Whitfield Peter C. , Guazzo Eric P. , Pickard John D.
Published: June 2009

✓ The authors describe a simple technique that reduces the incidence of retained ventricular catheters and minimizes the risk of life-threatening intraventricular hemorrhage during the removal of an obstructed, adherent ventricular catheter in patients with hydrocephalus. The technique requires no special equipment and has been successfully used, without complications, in a prospective series of 12 patients with 13 blocked, adherent ventricular catheters.
A tribute to Dr. A. Earl Walker
Authors: Udvarhelyi George B.
Published: June 2009

✓ Doctor Walker died on January 1, 1995, at the age of 87 years. His contributions to neuroscience and neurosurgery are presented and discussed, together with his impact on national and international organizations of neurosurgery. A short account of his background and professional career is given, with emphasis on his 25 years at The Johns Hopkins Hospital as Chief of Neurosurgery.
Ethanol, Corn, and Soybean Price Relations in a Volatile Vehicle-Fuels Market
Authors: Zhang Zibin , Lohr Luanne , Escalante Cesar , Wetzstein Michael
Published: June 2009

The rapid upward shift in ethanol demand has raised concerns about ethanol’s impact on the price level and volatility of agricultural commodities. The popular press attributes much of this volatility in commodity prices to a price bubble in ethanol fuel and recent deflation. Market economics predicts not only a softening of demand to high commodity prices but also a positive supply response. This volatility in ethanol and commodity prices are investigated using cointegration, vector error corrections (VECM), and multivariate generalized autoregressive conditional heteroskedascity (MGARCH) models. In terms of derived demand theory, results support ethanol and oil demands as derived demands from vehicle-fuel production. Gasoline prices directly influence the prices of ethanol and oil. However, of greater significance for the fuel versus food security issue, results support the effect of agricultural commodity prices as market signals which restore commodity markets to their equilibriums after a demand or supply event (shock). Such shocks may in the short-run increase agricultural commodity prices, but decentralized freely operating markets will mitigate the persistence of these shocks. Results indicate in recent years there are no long-run relations among fuel (ethanol, oil and gasoline) prices and agricultural commodity (corn and soybean) prices.
Chemical Analysis of the Resinous Exudate Isolated from Heliotropium taltalense and Evaluation of the Antioxidant Activity of the Phenolics Components and the Resin in Homogeneous and Heterogeneous Systems
Authors: Modak Brenda , Rojas Macarena , Torres René
Published: June 2009

H. taltalense (Phil.) Johnst. (Heliotropiaceae) is an endemic species of the northern coast of Chile that produces a resinous exudate that covers its foliar surface and stems. Its chemical composition was analyzed for the first time, and two aromatic geranyl derivatives: filifolinol and filifolinyl senecionate and three flavonoids – naringenin, 3-O-methylgalangin and 7-O-methyleriodictiol – were isolated. The antioxidant activity of the flavonoids and the resinous exudates was carried out by measuring the 1,1-diphenyl-2-picrylhydrazyl (DPPH) bleaching effect in ethanolic solution and in sodium dodecyl sulfate (SDS) micelles. The influence of the reaction medium was analyzed. The initial velocity reactions for the pure compounds and for the extract were higher in SDS media than in ethanolic solution. The velocity of reaction observed was interpreted in terms of the reaction medium environment in the micelle.
Global Oxygen Detection in Water Using Luminescent Probe on Anodized Aluminum
Authors: Sakaue Hirotaka , Ozaki Tatsuya , Ishikawa Hitoshi
Published: June 2009

We have developed anodized-aluminum pressure-sensitive paint (AA-PSP) as a global oxygen sensor in water. Platinum (II) meso-tetra(pentafluorophenyl)porphine is selected as a luminophore based on a dipping deposition study. The developed AA-PSP is characterized using water calibration setup by controlling dissolved oxygen concentration. It is shown that AA-PSP yields 4.0% change in luminescence per 1 mg/L of oxygen concentration at 23°C. Other characteristics, such as temperature dependency, photo-degradation, and physical stability, are discussed in this paper. This AA-PSP is used to demonstrate its capability of global oxygen detection in water using the impingement of oxygen rich water (20 mg/L). Even though the difference in water is only the concentration of oxygen, we can obtain global oxygen information of the jet impingement using a fast frame rate camera. Oxygen maps as well as cross-sectional distributions are shown every 0.1 s.
Fluorescence Detection and Discrimination of ss- and ds-DNA with a Water Soluble Oligopyrene Derivative
Authors: Chen Youqiang , Shi Gaoquan
Published: June 2009

A novel water-soluble cationic conjugated oligopyrene derivative, oligo(N1,N1,N1,N4,N4,N4-hexamethyl-2-(4-(pyren-1-yl) butane-1,4-diaminium bromide) (OHPBDB), was synthesized by a combination of chemical and electrochemical synthesis techniques. Each oligomer chain has five pyrene derivative repeating units and brings 10 positive charges. OHPBDB showed high and rapid fluorescence quenching in aqueous media upon addition of trace amounts of single-stranded (ss) and double-stranded (ds) DNA. The Stern-Volmer constants for ss- and ds-DNA were measured to be as high as 1.3 × 108 mol-1·L and 1.2 × 108 mol-1·L, respectively. On the other hand, distinct fluorescence enhancement of OHPBDB upon addition of large amount of ss-DNA or ds-DNA was observed. Furthermore, ss-DNA showed much stronger fluorescence enhancement than that of ds-DNA, thus yielding a clear and simple signal useful for the discrimination between ss- and ds-DNA in aqueous media.
Resolution improvement and noise reduction in human pinhole SPECT using a multi-ray approach and the SHINE method
Authors: Vanhove C. , Defrise M. , Seret A.
Published: June 2009

Purpose: This work aimed at quantifying the gains in spatial resolution and noise that could be achieved when using resolution modelling based on a multi-ray approach and additionally the Statistical and Heuristic Noise Extraction (SHINE) method in human pinhole single photon emission tomography (PH-SPECT). Methods: PH-SPECT of two line phantoms and one homogeneous cylinder were recorded using parameters suited for studies of the human neck area. They were reconstructed using pinhole dedicated ordered subsets expectation maximisation algorithm including a resolution recovery technique based on 7 or 21 rays. Optionally, the SPECT data were SHINE pre-processed. Transverse and axial full widths at half-maximum (FWHM) were obtained from the line phantoms. The noise was quantified using the coefficient of variation (COV) derived from the uniform phantom. Two human PHSPECT studies of the thyroid (a hot nodule and a very low uptake) were processed with the same algorithms. Results: Depending on the number of iterations, FWHM decreased by 30 to 50% when using the multi-ray approach in the reconstruction process. The SHINE method did not affect the resolution but decreased the COV by at least 20% and by 45% when combined with the multi-ray method. The two human studies illustrated the gain in spatial resolution and the decrease in noise afforded both by the multi-ray reconstruction and the SHINE method. Conclusion: Iterative reconstruction with resolution modelling allows to obtain high resolution human PH-SPECT studies with reduced noise content. The SHINE method affords an additional noise reduction without compromising the resolution.
The potential value of a pictorial atlas for aid in the visual diagnosis of 123I FP-CIT SPECT scans
Authors: Ham H. , Dobbeleir A. , Santens P. , D'Asseler Y. , Goethals I.
Published: June 2009

The aim of our study was to evaluate the value of a pictorial atlas of 123I FP-CIT SPECT images for aid in the visual diagnosis. Patients, materials, methods: Sixty patients, of whom 20 were clinically diagnosed as ‘non-parkinsonian’ and 40 as having Parkinson's disease or any related disorder, were included in the study. An atlas consisting of 12 123I FP-CIT SPECT images was constructed first. Validity of the atlas was investigated by performing a receiver operating characteristic (ROC) analysis with the clinical diagnosis as the gold standard. The remaining 48 SPECT images were visually assessed twice by 5 observers, first with and secondly without consulting the atlas, or vice versa. The added value of the atlas was investigated by comparing the diagnostic accuracy and the interobserver variability for both methods. Results: ROC analysis performed on the atlas yielded an area under the curve of 1 for a threshold discriminating between clinically non-parkinsonian and parkinsonian patients that was situated between image 4 and 5 of the atlas. For the diagnostic accuracy, we found that the area under the ROC curve was systematically higher if observers had access to the atlas compared to when they had not (Wilcoxon's test, p<0.05). Also, the interobserver variability was significantly lower when observers used the atlas when compared to when they did not (p = 0.05). Conclusion: Diagnostic accuracy was significantly higher and interobserver variability significantly lower if observers had access to the atlas compared to when they had not. Hence, having a pictorial atlas available may facilitate the visual assessment of 123I FP-CIT SPECT scans.
MIBI scintigraphy in hypofunctioning thyroid nodules
Authors: Schmidt M. , Ivanova T. , Dietlein M. , Schicha H. , Theissen P.
Published: June 2009

Aim: Several authors have investigated the value of technetium-MIBI scanning to predict the dignity of hypofunctioning, cold thyroid nodules (HTN) in regions with differing levels of iodine supply. They concluded that an MIBI scan can exclude thyroid malignancy, although comparisons between the studies are of limited value owing to differences in methodology and wide variations in patient selection criteria. The present study investigates whether the above claim is also valid in Germany, a country with a long-standing and persistent, mild iodine deficiency and a high incidence of nodules in large goiters with a low prevalence of malignancy. Patients, methods: The study compares the results of 99mTc-MIBI scintigraphy (incl. SPECT and planar images) in HTN (MIBI) with those of fine-needle aspiration biopsy (FNAB) and histology. Of 154 consecutive patients (121 women, 33 men; mean age 56 ± 12 years), 73 underwent thyroid surgery from which the results of FNAB and MIBI were assessed. Selection criteria were risk estimation or conditions limiting the feasibility of FNAB. The mean thyroid volume was 42 ± 25 ml, with 2.1 ± 1.4 nodules per patient. Results: Histology revealed thyroid malignancies in 8 out of 73 patients (11.0%). The negative predictive value for MIBI was 97%, which is comparable to FNAB (94%). However, in 19.5% of patients FNAB was indeterminate. Lower specificity (54%) and low positive predictive value (19%) showed that MIBI accumulation cannot differentiate between malignant and benign thyroid nodules. However, comparison with cytological and/or histological findings indicated that it could distinguish between lesions with differing rates of mitochondrial metabolism. Conclusion: Even in areas of former or mild iodine deficiency MIBI forms a basis for choosing between wait-and-see and surgical strategies if FNAB is unfeasible or not representative. However, even for pathological MIBI results, the prevalence of malignancy is not very high.
The development and evaluation of a continuous flow process for the lipase-mediated oxidation of alkenes
Authors: Wiles Charlotte , Hammond Marcus J , Watts Paul
Published: June 2009

We report the use of an immobilised form of Candida antarctica lipase B, Novozym® 435, in a preliminary investigation into the development of a continuous flow reactor capable of performing the chemo-enzymatic oxidation of alkenes in high yield and purity, utilising the commercially available oxidant hydrogen peroxide (100 volumes). Initial investigations focussed on the lipase-mediated oxidation of 1-methylcyclohexene, with the optimised reaction conditions subsequently employed for the epoxidation of an array of aromatic and aliphatic alkenes in 97.6 to 99.5% yield and quantitative purity.
Accuracy of Wallace Criteria for Clinical Remission in Juvenile Idiopathic Arthritis: a Cohort Study of 761 Consecutive Cases
Authors: LURATI ALFREDOMARIA , SALMASO ALESSANDRA , GERLONI VALERIA , GATTINARA MAURIZIO , FANTINI FLAVIO
Published: June 2009

Objective.

To evaluate disease course and clinical usefulness in some categories of juvenile idiopathic arthritis (JIA) by applying newly developed Wallace definitions of remission off drugs.

Methods.

In a retrospective study, charts of patients with chronic form of primary (idiopathic) arthritis followed from our center since 1970 were reviewed and clinical/laboratory variables were collected for further analysis.

Results.

The cohort included 761 eligible patients [516 (67.8%) female, 245 (32.2%) male] with JIA. Mean disease onset age (± standard deviation) was 6.25 ± 4.4 years (range 0.5–15.9). Disease mean duration to last visit was 10.02 ± 4.31 years. Followup mean period was 7.6 ± 6.4 years (range 1.5–35 yrs). A total of 247 (32.46%) patients achieved remission according to criteria [persistent oligoarthritis 153 (42.9%); extended oligoarthritis 15 (13.1%); seronegative polyarthritis 21 (22.4%); systemic arthritis 33 (33.7%); enthesitis related arthritis (ERA) plus juvenile psoriatic arthritis (JPsA) 25 (33.4%)]. No patients with seropositive polyarthritis achieved remission status (p < 0.001). In remitted patients the mean survival function (± standard error of the mean) before relapse calculated by Kaplan-Meier was of 20.9 (± 1.3) months overall: 21.7 (± 0.46) in persistent oligoarthritis, 25.0 (± 6.6) in extended oligoarthritis, 26.7 (± 13.2) in seronegative polyarthritis, and 17.6 (± 2.44) in ERA+JPsA (p > 0.1).

Conclusion.

In our cohort about one-third of cases obtained a remission episode in 4 decades of observation, with a significant difference between oligoarthritis and other categories (p < 0.001) using the Kaplan-Meier method; the remission status duration before a relapse has been about 20 months, without a significant difference between JIA categories.
E-selectin, Interleukin 18, Serum Amyloid A, and Matrix Metalloproteinase 9 Are Associated with Clinical Response to Golimumab plus Methotrexate in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy
Authors: VISVANATHAN SUDHA , WAGNER CARRIE , ROJAS JEANNIE , KAY JONATHAN , DASGUPTA BHASKAR , MATTESON ERIC L. , MACK MICHAEL , BAKER DANIEL G. , RAHMAN MAHBOOB U.
Published: June 2009

Objective.

To assess the effect of golimumab (human monoclonal antibody to tumor necrosis factor-α) plus methotrexate (MTX) on selected inflammatory biomarkers, and to determine if these effects predict clinical response in rheumatoid arthritis (RA).

Methods.

Sera from adults with active RA despite MTX therapy, who received subcutaneous injections of placebo + MTX (MTX alone, n = 34) or golimumab 50 or 100 mg every 2 or 4 weeks + MTX (n = 137), were analyzed for levels of C-reactive protein (CRP), serum amyloid A (SAA), interleukin 18 (IL-18), E-selectin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1).

Results.

Golimumab + MTX treatment significantly decreased serum CRP, SAA, IL-18, E-selectin, TIMP-1, and MMP-9 levels (median percent changes of −4.1% to −74.3% across treatment groups) versus MTX alone (−5.8% to 9.7%) when first measured at Week 4; decreases were sustained through Week 16. Larger magnitudes of decrease in all biomarkers were observed for clinical responders versus nonresponders. For golimumab + MTX, regression analyses including all biomarkers and select clinical measures showed that reductions in levels of several markers (SAA, E-selectin, MMP-9) as early as Week 4 correlated significantly with improvement in swollen joint count (SJC) at Week 16, as did reductions in E-selectin with improvement in tender joint count at Week 16. After accounting for the biomarkers, however, treatment group was no longer significant for SJC.

Conclusion.

Significant decreases in several inflammatory biomarkers were associated with golimumab + MTX therapy. Decreases in serum levels of SAA, E-selectin, and MMP-9 at Week 4 may be useful in predicting clinical response at Week 16.
Preventing Tuberculosis Flare in Patients with Inflammatory Rheumatic Diseases Receiving Tumor Necrosis Factor-α Inhibitors in India — An Audit Report
Authors: MALAVIYA ANAND N. , KAPOOR SANJIV , GARG SHRIRAM , RAWAT ROOPA , SHANKAR SUBRAMANIAN , NAGPAL SAVITA , KHANNA DINESH , FURST DANIEL E.
Published: June 2009

Objective.

To test the efficacies of a strategy for preventing tuberculosis (TB) in Indian patients with inflammatory rheumatic diseases (IRD) treated with tumor necrosis factor-α (TNF-α) inhibitor.

Methods.

The screening strategy included tuberculosis skin test (TST), QuantiFERON-TB Gold (QTG) test, standard chest radiograph, and contrast enhanced-computerized tomography of the chest (CT).

Results.

Among 53 patients screened, 17 (32%) had ≥ 1 test positive, with 5 (9.4%) patients having TB infection (clinical, CT, biopsy). The remaining 12 patients showed latent TB; 1 additional patient with negative screening tests was diagnosed with latent TB retrospectively for he developed TB disease within a few weeks of receiving infliximab. The remaining 35 patients tested negative with all tests. The combination of 4 screening tests gave a sensitivity of 0.83, specificity of 0.74, positive predictive value (PPV) 0.29, and negative predictive value (NPV) 0.97. Only 22 patients could afford treatment with TNF-α inhibitors; 19 of them were negative in the screening tests. Three patients who were positive on TST and/or QTG received prophylactic treatment with TNF-α inhibitor. Since implementation of the screening strategy, only 1 of 22 (4.5%) patients given TNF-α inhibitor developed probable TB disease.

Conclusion.

With the use of these 4 TB screening tests in India, where TB is highly prevalent, TB could be excluded with a high degree of certainty (NPV 0.97). However, as even this combination of tests has only moderate sensitivity and specificity and poor PPV for detecting TB, vigilance may be advisable even if only one of the tests is positive.
Validity of Self-Reported Comorbidities in Systemic Sclerosis: Table 1.
Authors: HUDSON MARIE , SHARMA ANISH , BERNSTEIN JESSICA ,   the CANADIAN SCLERODERMA RESEARCH GROUP, BARON MURRAY
Published: June 2009

Objective.

To assess the validity of self-reports by patients with systemic sclerosis (SSc) of 5 common, chronic conditions (hypertension, diabetes, cancer, depression, and osteoarthritis/back pain) as compared to chart review.

Methods.

SSc patients at a large referral hospital self-reported on a number of comorbidities. Their inpatient and outpatient medical records were abstracted using a standardized data extraction form. Sensitivity, specificity, and positive predictive value of the self-reported diagnoses were calculated using data from the chart review as gold standard.

Results.

Self-reported comorbidity data were verified by chart review for 130 patients with SSc. The sensitivity of the self-reports for the 5 comorbid conditions was low [range 35% (cancer) to 86% (diabetes)]. The specificity was moderate to high [range 76% (osteoarthritis/back pain) to 99% (cancer)]. The positive predictive values ranged from 31% (depression) to 86% (cancer).

Conclusion.

Self-reports of comorbidities do not provide optimal data for the identification of common, chronic conditions in patients with SSc.
Spontaneous Outcropping of Self‐Assembled Insulating Nanodots in Solution‐Derived Metallic Ferromagnetic La0.7Sr0.3MnO3 Films
Authors: Moreno César , Abellán Patricia , Hassini Awatef , Ruyter Antoine , del Pino Angel Pérez , Sandiumenge Felip , Casanove Marie‐Jose , Santiso José , Puig Teresa , Obradors Xavier
Published: June 2009

A new mechanism is proposed for the generation of self‐assembled nanodots at the surface of a film based on spontaneous outcropping of the secondary phase of a nanocomposite epitaxial film. Epitaxial self‐assembled Sr–La oxide insulating nanodots are formed through this mechanism at the surface of an epitaxial metallic ferromagnetic La0.7Sr0.3MnO3 (LSMO) film grown on SrTiO3 from chemical solutions. TEM analysis reveals that, underneath the La–Sr oxide (LSO) nanodots, the film switches from the compressive out‐of‐plane stress component to a tensile one. It is shown that the size and concentration of the nanodots can be tuned by means of growth kinetics and through modification of the La excess in the precursor chemical solution. The driving force for the nanodot formation can be attributed to a cooperative effect involving the minimization of the elastic strain energy and a thermodynamic instability of the LSMO phase against the formation of a Ruddelsden–Popper phase Sr3Mn4O7 embedded in the film, and LSO surface nanodots. The mechanism can be described as a generalization of the classical Stranski–Krastanov growth mode involving phase separation. LSO islands induce an isotropic strain to the LSMO film underneath the island which decreases the magnetoelastic contribution to the magnetic anisotropy.
The Synthesis and Assembly of Polymeric Microparticles Using Microfluidics
Authors: Dendukuri Dhananjay , Doyle Patrick S.
Published: June 2009

The controlled synthesis of micrometer‐sized polymeric particles bearing features such as nonspherical shapes and spatially segregated chemical properties is becoming increasingly important. Such particles can enable fundamental studies on self‐assembly and suspension rheology, as well as be used in applications ranging from medical diagnostics to photonic devices. Microfluidics has recently emerged as a very promising route to the synthesis of such polymeric particles, providing fine control over particle shape, size, chemical anisotropy, porosity, and core/shell structure. This progress report summarizes microfluidic approaches to particle synthesis using both droplet‐ and flow‐lithography‐based methods, as well as particle assembly in microfluidic devices. The particles formed are classified according to their morphology, chemical anisotropy, and internal structure, and relevant examples are provided to illustrate each of these approaches. Emerging applications of the complex particles formed using these techniques and the outlook for such processes are discussed.