bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional polymorphism of the NFKB1 gene promoter is related to the risk of dilated cardiomyopathy
Authors: Zhou Bin , Rao Li , Peng Ying , Wang Yanyun , Li Yi , Gao Linbo , Chen Yu , Xue Hui , Song Yaping , Liao Miao , Zhang Lin
Published: June 2009

Background

Previous studies in experimental and human heart failure showed that nuclear factor kappa B (NF-κB) is chronically activated in cardiac myocytes, suggesting an important involvement of NF-κB in the cardiac remodeling process. A common insertion/deletion (-94 insertion/deletion ATTG, rs28362491) located between two putative key promoter regulatory elements in the NFKB1 gene was identified which seems to be the first potential functional NFKB1 genetic variation. The main goal of the present investigation was to investigate the NFKB1 -94 insertion/deletion ATTG polymorphism in relation to risk of dilated cardiomyopathy (DCM).

Methods

A total of 177 DCM patients and 203 control subjects were successfully investigated. The NFKB1 -94 insertion/deletion ATTG polymorphism was genotyped by using PCR-PAGE.

Results

Genotype frequency of NFKB1 -94 insertion/deletion ATTG polymorphism in DCM patients was significantly different from that in control subjects (P = 0.015) and the ATTG2 carrier (ATTG1/ATTG2 + ATTG2/ATTG2) was susceptible to DCM.

Conclusion

Our data suggested that NFKB1 -94 insertion/deletion ATTG polymorphism is associated with DCM.
Stem cell factor and its soluble receptor (c-kit) in serum of asthmatic patients- correlation with disease severity
Authors: Makowska Joanna S , Cieslak Malgorzata , Kowalski Marek L
Published: June 2009

Background

SCF (stem cell factor) is a pleiotropic cytokine exerting its role at different stages of bone marrow development and affecting eosinophil activation, mast cells and basophil chemotaxis and survival. The aim of the study was to assess concentration of SCF and its soluble receptor c-kit (sc-kit) in peripheral blood of patients with asthma referring it to asthma severity and phenotype.

Methods

The study involved 107 patients with bronchial asthma, well characterized with respect to severity and 21 healthy controls. Concentration of SCF and sc-kit in the patients serum were measured by ELISA method.

Results

Mean serum SCF level in the group of asthmatics (n = 88) was significantly higher as compared to healthy controls (1010 pg/ml ± 37 vs 799 ± 33; p < 0,001). The level of SCF was higher in patients with severe asthma as compared to patients with non-severe asthma (1054 +/- 41 pg/ml vs 819 +/- 50; p < 0,01) and correlated with dose of inhaled glucocorticosteroids taken by the patients to achieve asthma control (R = 0,28; p < 0,01). The mean sc-kit serum level did not differ between asthmatic patients and healthy controls, however the level of sc-kit in non-severe asthmatics was significantly higher as compared to patients with severe asthma and healthy controls. In asthmatic patients (n = 63) the level of sc-kit correlated positively with FEV1% predicted value (R = 0,45; p < 0,001) and MEF25% predicted value (R = 0,33; p < 0,01). The level of sc-kit inversely correlated with the dose of inhaled glucocorticosteroids taken by the patients (R = -0,26; p < 0,01).

Conclusion

Serum levels of SCF and its soluble receptor c-kit seem to be reflect asthma severity suggesting a role for these molecules in asthmatic inflammation.
An alternative methodology for the prediction of adherence to anti HIV treatment
Authors: Thompson IRichard , Bidgood Penelope , Petróczi Andrea , Denholm-Price James CW , Fielder Mark D ,   The Eu Resist Network Study Group
Published: June 2009

Background

Successful treatment of HIV-positive patients is fundamental to controlling the progression to AIDS. Causes of treatment failure are either related to drug resistance and/or insufficient drug levels in the blood. Severe side effects, coupled with the intense nature of many regimens, can lead to treatment fatigue and consequently to periodic or permanent non-adherence. Although non-adherence is a recognised problem in HIV treatment, it is still poorly detected in both clinical practice and research and often based on unreliable information such as self-reports, or in a research setting, Medication Events Monitoring System caps or prescription refill rates. To meet the need for having objective information on adherence, we propose a method using viral load and HIV genome sequence data to identify non-adherence amongst patients.

Presentation of the hypothesis

With non-adherence operationally defined as a sharp increase in viral load in the absence of mutation, it is hypothesised that periods of non-adherence can be identified retrospectively based on the observed relationship between changes in viral load and mutation.

Testing the hypothesis

Spikes in the viral load (VL) can be identified from time periods over which VL rises above the undetectable level to a point at which the VL decreases by a threshold amount. The presence of mutations can be established by comparing each sequence to a reference sequence and by comparing sequences in pairs taken sequentially in time, in order to identify changes within the sequences at or around 'treatment change events'. Observed spikes in VL measurements without mutation in the corresponding sequence data then serve as a proxy indicator of non-adherence.

Implications of the hypothesis

It is envisaged that the validation of the hypothesised approach will serve as a first step on the road to clinical practice. The information inferred from clinical data on adherence would be a crucially important feature of treatment prediction tools provided for practitioners to aid daily practice. In addition, distinct characteristics of biological markers routinely used to assess the state of the disease may be identified in the adherent and non-adherent groups. This latter approach would directly help clinicians to differentiate between non-responding and non-adherent patients.
Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202
Authors: Sanuki-Fujimoto Naoko , Ishikura Satoshi , Hayakawa Kazushige , Kubota Kaoru , Nishiwaki Yutaka , Tamura Tomohide
Published: June 2009

Background

The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG.

Methods

JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy/30 fx (bis in die, BID/twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE).

Results

A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased.

Conclusion

The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results.
Menstrual Cycle and Surgical Treatment of Breast Cancer: Findings From the NCCTG N9431 Study
Authors: Grant Clive S. , Ingle James N. , Suman Vera J. , Dumesic Daniel A. , Wickerham D. Lawrence , Gelber Richard D. , Flynn Patrick J. , Weir Lorna M. , Intra Mattia , Jones Wayne O. , Perez Edith A. , Hartmann Lynn C.
Published: June 2009

Purpose

For nearly two decades, multiple retrospective reports, small prospective studies, and meta-analyses have arrived at conflicting results regarding the value of timing surgical intervention for breast cancer on the basis of menstrual cycle phase. We present the results of a multi–cooperative group, prospective, observational trial of menstrual cycle phase and outcome after breast cancer surgery, led by the North Central Cancer Treatment Group (NCCTG) in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the International Breast Cancer Study Group (IBCSG).

Patients and Methods

Premenopausal women age 18 to 55 years, who were interviewed for menstrual history and who were surgically treated for stages I to II breast cancer, had serum drawn within 1 day of surgery for estradiol, progesterone, and luteinizing hormone levels. Menstrual history and hormone levels were used to determine menstrual phase: luteal, follicular, and other. Disease-free survival (DFS) and overall survival (OS) rates were determined by Kaplan-Meier method and were compared by using the log-rank test and Cox proportional hazard modeling.

Results

Of 1,118 women initially enrolled, 834 women comprised the study cohort: 230 (28%) in luteal phase; 363 (44%) in follicular phase; and 241 grouped as other. During a median follow-up of 6.6 years, and in analysis that accounted for nodal disease, estrogen receptor status, adjuvant radiation therapy or chemotherapy, neither DFS nor OS differed with respect to menstrual phase. The 5-year DFS rates were 82.7%, 82.1%, and 79.2% for follicular, luteal, or other phases, respectively. Corresponding OS survival rates were 91.9%, 92.2%, and 91.8%, respectively.

Conclusion

When menstrual cycle phases were strictly defined, neither DFS nor OS differed between women who underwent surgery during the follicular phase versus the luteal phase. Nearly 30% of the patients did not meet criteria for either follicular- or luteal-phase categories.
In Cinderella's Shoes
Authors: Popescu Marian
Published: June 2009

Romanian theater critic and scholar Marian Popescu discusses the challenges faced by Romanian playwrights, directors, and other theater practitioners since the fall of communism. He details the struggles that artists and institutions have had to address and adjust to since the end of the Ceaucescu regime, as well as efforts of Romanian artists to create new forms and engage in the world theater scene.
The Old Road Rapidly Aging
Authors: Modreanu Cristina
Published: June 2009

Romanian theater scholar Cristina Modreanu discusses the primary model of dramaturgy, classical texts presented in a realistic style, has evolved after 1989 in Romania to accommodate new visual styles of avant-garde directors. Modreanu describes directors such as Mihail Maniutiu, Alexandru Tocilescu, Gabor Tompa, Victor Ioan Frunza, and Alexander Hausvater as artistic “survivors” of the old regime, while Silviu Purcarete represents the present and future of Romanian theater.
Clap If You Want To
Authors: Penescu Razvan
Published: June 2009

In this personal essay, Romanian publisher (LiterNet.ro) Razvan Penescu writes about his decision not to applaud a poor performance at the National Theater of Bucharest and how his dissent represents an expressive freedom that was disallowed in communist Romania.
Things that Have to Do with Us
Authors: Nelega Alina
Published: June 2009

Alina Nelega offers a playwright's perspective on the development of playwriting in post-communist Romania. She details the challenges faced by new playwrights in a primarily visual, director-driven theatrical culture, and discusses the history of programs like Dramafest and dramAcum, designed to foster new writing. Particular attention is paid to writers Gianina Carbinariu and Stefan Peca.
Sopron – Nové Košariská – Frög. Zu den Bildgeschichten der Kalenderberg-Kultur
Authors: Gleirscher Paul
Published: June 2009

Ein im Jahre 2002 ergrabenes Kegelhalsgefäß aus dem hallstattzeitlichen Hügelgräberfeld von Frög bei Rosegg (Kärnten) zeigt ausgewählte Bilder, wie sie seit langem aus dem Bereich der Kalenderberg-Kultur bekannt sind. Sechs Paare von Tänzern – männlich, weiblich bzw. Mann und Frau – umrahmen das zentrale Bild. Es besteht aus zwei übergroß dargestellten und stark stilisierten Frauen, denen drei kleinere Frauen und ein Stier samt Hund als Chiffre für eine Jagdszene zuzuordnen sind. Zwischen den Menschen und Tieren befinden sich verschiedenartige Spiralmotive und Rosetten. Die Regelhaftigkeit der Chiffren legt die Vorstellung eines standardisierten Rituals oder ein und derselben Geschichte nahe. Doch muss letztlich offen gelassen werden, ob die wiedergegebenen Bilder tatsächlich den Kern des Rituals bzw. einer oder mehrerer Geschichten zeigen oder als dessen bzw. deren Rahmenbilder zu verstehen sind.
Short‐Term Effects of an Anti‐Inflammatory Treatment on Clinical Parameters and Serum Levels of C‐Reactive Protein and Proinflammatory Cytokines in Subjects With Periodontitis
Authors: Renvert Stefan , Lindahl Christel , Roos‐Jansåker Ann‐Marie , Lessem Jan
Published: June 2009

Background: Periodontal disease is the most common multifactorial disease, afflicting a very large proportion of the adult population. Periodontal disease secondarily causes increases in the serum levels of C‐reactive protein (CRP) and other markers of inflammation. An increased level of CRP reflects an increased risk for cardiovascular disease. The aim of the current randomized clinical trial was to evaluate the short‐term effect of a combination of dipyridamole and prednisolone (CRx‐102) on the levels of high‐sensitivity (hs)‐CRP, proinflammatory markers in blood, and clinical signs of periodontal disease.

Methods: Fifty‐seven patients with ≥10 pockets with probing depths ≥5 mm were randomized into two groups in this masked single‐center placebo‐controlled study: CRx‐102 (n = 28) and placebo (n = 29). hs‐CRP levels, inflammatory markers (interleukin [IL]‐6, −1β, −8, and −12, tumor necrosis factor‐alpha, and interferon‐gamma [IFN‐γ]), bleeding on probing (BOP), and changes in probing depths were evaluated. The subjects received mechanical non‐surgical therapy after 42 days, and the study was completed after 49 days.

Results: At day 42, the differences in the hs‐CRP, IFN‐γ, and IL‐6 levels between the two groups were statistically significant (P <0.05), whereas no difference was found for the other inflammatory markers. There was no change in probing depth or BOP between the two groups.

Conclusion: The administration of CRx‐102 resulted in significant decreases in hs‐CRP, IFN‐γ, and IL‐6, but it did not significantly change BOP or probing depths.
A Surgical Reentry Study on the Influence of Platelet‐Rich Plasma in Enhancing the Regenerative Effects of Bovine Porous Bone Mineral and Guided Tissue Regeneration in the Treatment of Intrabony Defects in Humans
Authors: Camargo Paulo M. , Lekovic Vojislav , Weinlaender Michael , Divnic‐Resnik Tihana , Pavlovic Marija , Kenney E. Barrie
Published: June 2009

Background: The purpose of this study was to evaluate the additional benefits provided by the incorporation of platelet‐rich plasma (PRP) into a regenerative protocol consisting of bovine porous bone mineral (BPBM) and guided tissue regeneration (GTR) in the treatment of intrabony defects in humans.

Methods: Twenty‐three paired intrabony defects were surgically treated using a split‐mouth design. Defects were treated with BPBM/GTR/PRP (experimental group) or with BPBM/GTR (control group). The clinical parameters evaluated included changes in probing depth, clinical attachment level, and defect fill as revealed by reentry surgeries at 6 months.

Results: Preoperative probing depths, attachment levels, and transoperative bone measurements were similar for the two groups. Post‐surgical measurements taken at 6 months revealed that both treatment modalities resulted in a significant decrease in probing depth, gain in clinical attachment, and bone fill of the defects compared to baseline. Postoperative differences observed between the two groups were 0.72 ± 0.36 mm at buccal sites and 0.90 ± 0.32 mm at lingual sites for probing depth, 0.82 ± 0.41 mm at buccal sites and 0.78 ± 0.38 at lingual sites for gain in clinical attachment, and 0.85 ± 0.36 mm at buccal sites and 0.94 ± 0.42 mm at lingual sites for defect fill, all favoring the experimental sites. However, none of the differences were statistically significant.

Conclusion: Within the limitations related to using a small sample size, PRP did not significantly augment the effects of BPBM and GTR in promoting the clinical resolution of intrabony defects.
Fetal Exposure to Oral Pathogens and Subsequent Risk for Neonatal Intensive Care Admission
Authors: Jared Heather , Boggess Kim A. , Moss Kevin , Bose Carl , Auten Richard , Beck James , Offenbacher Steven
Published: June 2009

Background: Maternal periodontal infection has been associated with adverse maternal and neonatal outcomes. In utero fetal exposure to oral pathogens was also recognized as deleterious to the fetus. The objective of this study was to determine the relationship between fetal exposure to oral pathogens and neonatal intensive care unit (NICU) admission.

Methods: This was a secondary analysis of a prospective cohort study of maternal oral health and pregnancy outcome. Fetal immunoglobulin M against oral pathogens was detected in umbilical cord serum by immunoblot. The presence of at least one oral pathogen–specific antibody was considered seropositivity. The cord level of C‐reactive protein was determined by enzyme‐linked immunosorbent assay and categorized as detectable versus undetectable. Chi‐square and logistic regression analyses were used to determine the association between cord serum seropositivity or detectable C‐reactive protein and NICU admission and length of stay.

Results: Of 650 infants, 45 (6.9%) were admitted to the NICU. The admission rate was higher among seropositive infants compared to seronegative infants (11% versus 5%; P = 0.0019). Seropositive infants were also more likely than seronegative infants to stay >3 or >7 days (8% versus 3% and 6% versus 2%; P = 0.004 and 0.003, respectively). Adjusting for gestational age, the odds ratio (95% confidence interval) for NICU admission was 2.14 (1.01 to 4.54); for a length of stay >3 or >7 days, it was 2.38 (1.01 to 5.60) and 3.29 (1.13 to 9.58), respectively. The NICU admission rate was not significantly higher for those with detectable versus undetectable umbilical cord serum C‐reactive protein (8% versus 6%; P = 0.3).

Conclusions: In utero fetal exposure to oral pathogens increases the risk for NICU admission and the length of stay. Interventions that interrupt fetal exposure to oral pathogens may reduce these risks.
Model theory without choice? Categoricity
Authors: Shelah Saharon
Published: June 2009

We prove Los conjecture = Morley theorem in ZF. with the same characterization, i.e., of first order countable theories categorical in ℵα for some (eqiuvalently for every ordinal) α > 0. Another central result here in this context is: the number of models of a countable first order T of cardinality ℵα is either ≥ ∣α∣ for every α or it has a small upper bound (independent of α close to ⊐2).
Projective prewellorderings vs projective wellfounded relations
Authors: Shi Xianghui
Published: June 2009

We show that it is relatively consistent with ZFC that there is aprojective wellfounded relation with rank higher than all projective prewellorderings.
Large cardinals and definable well-orders on the universe
Authors: Brooke-Taylor Andrew D.
Published: June 2009

We use a reverse Easton forcing iteration to obtain a universe with a definable well-order, while preserving the GCH and proper classes of a variety of very large cardinals. This is achieved by coding using the principle , at a proper class of cardinals κ. By choosing the cardinals at which coding occurs sufficiently sparsely, we are able to lift the embeddings witnessing the large cardinal properties without having to meet any non-trivial master conditions.
Two questions from Dana Scott: Intuitionistic topologies and continuous functions
Authors: McCarty Charles
Published: June 2009

Since intuitionistic sets are not generally stable – their membership relations are not always closed under double negation – the open sets of a topology cannot be recovered from the closed sets of that topology via complementation, at least without further ado. Dana Scott asked, first, whether it is possible intuitionistically for two distinct topologies, given as collections of open sets on the same carrier, to share their closed sets. Second, he asked whether there can be intuitionistic functions that are closed continuous in that the inverse of every closed set is closed without being continuous in the usual, open sense. Here, we prove that, as far as intuitionistic set theory is concerned, there can be infinitely-many distinct topologies on the same carrier sharing a single collection of closed sets. The proof employs Heyting-valued sets, and demonstrates that the intuitionistic set theory IZF [4, 624], as well as the theory IZF plus classical elementary arithmetic, are both consistent with the statement that infinitely many topologies on the set of natural numbers share the same closed sets. Without changing models, we show that these formal theories are also consistent with the statement that there are infinitely many endofunctions on the natural numbers that are closed continuous but not open continuous with respect to a single topology.

For each prime k ∈ ω, let Ak be this ω-sequence of sets open in the standard topology on the closed unit interval: for each n ∈ ω,
Transfection with bFGF sense and antisense cDNA resulting in modification of malignant glioma growth
Authors: Redekop Gary J. , Naus Christian C. G.
Published: June 2009

✓ Aberrant autocrine control by peptide growth factors is a possible mechanism by which disordered regulation of cell proliferation may occur. The authors used the C6 glioma cell line as a model to study the role of basic fibroblast growth factor (bFGF) in tumor growth by transfection with bFGF complementary deoxyribonucleic acid in both the sense and antisense orientation. Clones with high messenger ribonucleic acid expression of the sense construct have increased proliferation in cell culture and increased levels of intracellular and extracellular bFGF. Clones with high expression of the antisense construct show decreased proliferation in culture and reduced levels of immunologically detectable bFGF.
Accurate placement of the atrial catheter in ventriculoatrial shunts
Authors: Thompson Dominic N. P. , Casey Adrian T. , Hayward Richard D. , Harkness William F.
Published: June 2009

✓ A combined radiological and surgical technique that permits identification of appropriate recipient vessels and accurate placement of the atrial catheter in ventriculoatrial shunts is described. The procedure uses readily available radiological skills and reduces operation time and morbidity related to malpositioning of the distal catheter.
The effect of hemoglobin and its metabolites on energy metabolism in cultured cerebrovascular smooth-muscle cells
Authors: Nagatani Kazuhiko , Masciopinto Jeffery E. , Letarte Peter B. , Haworth Robert A. , Duff Thomas A.
Published: June 2009

✓ Cerebral arteries in spasm have been found to contain low levels of adenosine triphosphate (ATP), and it has been postulated that this change in levels results from hypoxia produced by arterial encasement in clotted material. This study was undertaken to determine whether any of four blood-derived agents, ferrous hemoglobin, methemoglobin, hemin, or bilirubin, is capable of reducing energy levels in cerebral artery smooth-muscle cells.

Twenty-four-hour exposure of cultured canine basilar artery cells to ferrous hemoglobin and bilirubin led to a significant decline in ATP levels (to 8.9 nmol/mg protein and 2.8 nmol/mg protein, respectively) versus control (16.6 nmol/mg protein); methemoglobin and hemin showed no effect. Bilirubin but not hemoglobin was found to interfere with electron transport and with creatine phosphokinase activity in intact cells; however, bilirubin showed no inhibitory effect on this enzyme in cell-free conditions. The findings indicate that hemoglobin and bilirubin may be responsible for diminished energy levels in cerebral arteries. These observations also suggest that bilirubin may exert its effect on ATP by impairing mitochondrial function.
Nonvisualization of a large cerebral aneurysm despite highresolution magnetic resonance angiography
Authors: Turtz Alan , Allen David , Koenigsberg Robert , Goldman H. Warren
Published: June 2009

✓ The use of magnetic resonance (MR) angiography as a safe, accurate, and reliable substitute for invasive cerebral arteriography has been anticipated as refinements in this technique are introduced. We present the case of an unruptured, 11-mm pericallosal arterial aneurysm not visualized on high-resolution MR angiography. Although this case may be atypical, we caution against complete reliance on this test for exclusion of the presence of cerebral aneurysms.
A guide to placement of parietooccipital ventricular catheters
Authors: Howard Matthew A. , Srinivasan Jayashree , Bevering Carl G. , Winn H. Richard , Grady M. Sean
Published: June 2009

✓ Accurate placement of parietooccipital ventricular catheters can be difficult and frustrating. To minimize the morbidity of the procedure and lengthen the duration of shunt function, the catheter tip should lie in the ipsilateral frontal horn. The authors describe a posterior ventricular guide (PVG) for placement of parietooccipital catheters that operates by mechanically coupling the posterior burr hole to the anterior target point. In a series of 38 patients who underwent ventriculoperitoneal shunting with the assistance of the guide, postoperative computerized tomography (CT) scanning revealed that 35 (92.0%) had accurate catheter placement. In comparison, a retrospective review of free-hand posterior catheter placement revealed good catheter position in only 22 of 43 patients (51.1%). The use of the guide added less than 5 minutes to the entire procedure, and there were no complications related to its use. The PVG is a simple and useful tool that aids in the placement of parietooccipital ventricular catheters.
Phase II evaluation of recombinant interferon alpha and BCNU in recurrent glioma
Authors: Buckner Jan C. , Brown Loren D. , Kugler John W. , Cascino Terrence L. , Krook James E. , Mailliard James A. , Kardinal Carl G. , Tschetter Loren K. , O'Fallon Judith R. , Scheithauer Bernd W.
Published: June 2009

✓ The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus recombinant interferon-alpha (IFN-a) in patients with recurrent glioma. As single agents, both BCNU and IFN-α can cause tumor regression in patients with recurrent glioma. In vitro studies suggest synergy between the two agents. Thirty-five patients in whom computerized tomography (CT) or magnetic resonance (MR) evidence was obtained of progressive astrocytoma, oligoastrocytoma, or oligodendroglioma received recombinant IFN-α2a (12 × 106 U/m2 intramuscularly) on Days 1 through 3 and BCNU (150 mg/m2 intravenously) on Day 3 of each 6-week cycle. All patients had tumor progression despite radiation therapy and had received no prior chemotherapy. Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids. All patients could be evaluated for response and toxicity. Twenty-nine percent of the patients demonstrated objective tumor regression; 37% remained stable for more than 6 months and 25% were stable for less than 6 months. The median duration of response to IFN-α and BCNU was 9.9 months and the median survival for all patients was 13.3 months. Toxicity consisted primarily of moderate myelosuppression, venous irritation, vomiting, flulike symptoms, and transient reversible exacerbation of underlying neurological symptoms. The use of BCNU plus IFN-α is a safe, active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy. The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone cannot be assessed from this trial.
Preoperative localization of brain lesions by magnetic resonance imaging with a marking device
Authors: Tanaka Shigeya , Uetsuhara Koichi , Tomosugi Tetsuzou , Moroki Kouichi , Yamada Masahiko , Toujou Hideshi , Kawakami Hideo , Sameshima Munetoshi
Published: June 2009

✓ A new technique for preoperative localization of brain lesions using magnetic resonance imaging and a marking device is described. The projection of lesions, especially superficial brain tumors, is demonstrated on the scalp, with an acceptable tolerance for open procedures. This simple and inexpensive method, which was used in a group of 34 patients, can assist surgeons in planning an operative approach to intracranial lesions.
Symptomatic syringomyelia following surgery to treat retethering of lipomyelomeningoceles
Authors: Chapman Paul H. , Frim David M.
Published: June 2009

✓ The authors report the cases of three children in whom symptomatic syringomyelia occurredde novo following an operation to relieve retethering of a previously treated lipomyelomeningocele. No patient had a Chiari malformation. In two cases, magnetic resonance imaging performed before the first operation did not show a syrinx. At the time of surgery to relieve retethering, it was discovered that one of these patients had a minor degree of terminal hydromyelia and the other had a prominent central canal within the conus medullaris. The third patient was initially studied by means of myelography, which gave no indication of a syrinx, and one was not found at the time of the surgery to release the retethering. Neurological deficits appeared abruptly within several months of operation in two children, and insidiously after 12 to 18 months in the other symptomatic individual. In all three cases, the syrinx involved the distal spinal cord adjacent to the site of the lipoma. Treatment consisted of syringosubarachnoid shunting, which arrested the progression of deficits but only partially reversed them. The details of each case are presented and the possible mechanism of syrinx formation discussed. Early recognition and treatment of this unusual but important problem are emphasized.
Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF
Authors: Tsai Jui-Chang , Goldman Corey K. , Gillespie G. Yancey
Published: June 2009

✓ Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an endothelial cell—specific mitogen that is structurally related to platelet-derived growth factor (PDGF). Vascular endothelial growth factor/vascular permeability factor induces angiogenesis in vivo and may play a critical role in tumor angiogenesis. Using immunohistochemical analysis, the authors demonstrated the presence of VEGF/VPF protein in surgical specimens of glioblastoma multiforme and cultured glioma cells. By means of an enzyme-linked immunosorbent assay (ELISA) of cell supernatants, the authors showed that VEGF/VPF is variably secreted by all nine cultured human malignant glioma cell lines (CH-235MG, D-37MG, D-54MG, D-65MG, U-87MG, U-105MG, U-138MG, U-251MG, U-373MG) and by a single meningioma cell line (CH-157MN). An immunocytochemical survey of these cell lines revealed a cytoplasmic and cell-surface distribution of VEGF/VPF. In the U-105MG glioma cell line, VEGF/VPF secretion was induced with physiological concentrations of epidermal growth factor, PDGF-BB, or basic fibroblast growth factor, but not with PDGF-AA. Moreover, it was observed that activation of convergent growth factor signaling pathways led to increased glioma VEGF secretion. Similar results were obtained using these growth factor combinations in the D-54MG glioma cell line. The data obtained suggest a potential role for VEGF/VPF in tumor hypervascularity and peritumoral edema. These observations may lead to development of new therapeutic strategies.
Prolactin-producing pituitary tumor: resistance to dopamine agonist therapy
Authors: Kovacs Kalman , Stefaneanu Lucia , Horvath Eva , Buchfelder Michael , Fahlbusch Rudolph , Becker Wolfgang
Published: June 2009

✓ A 14-year-old girl presented with a rapidly growing, invasive prolactin-producing pituitary tumor that failed to respond to dopamine agonist medication. Histological, immunocytochemical, and ultrastructural studies of the surgically removed tissue revealed a pleomorphic, chromophobic, or slightly acidophilic pituitary tumor that was immunoreactive for prolactin and that, according to electron microscopy, consisted of atypical lactotrophs showing no evidence of cell shrinkage.In situ hybridization demonstrated large amounts of prolactin messenger ribonucleic acid (mRNA), moderate amounts of estrogen receptor mRNA and dopamine (D2) receptor mRNA, and an absence of growth hormone mRNA in the tumor cells. Because D2 receptor mRNA was present in the tumor, causes other than D2 receptor loss may have been responsible for the resistance of the lactotrophs to dopamine agonist administration.
The use of magnetic resonance angiography in stereotactic neurosurgery
Authors: Michiels Johan , Bosmans Hilde , Nuttin Bart , Knauth Michael , Verbeeck Rudi , Vandermeulen Dirk , Wilms Guy , Marchal Guy , Suetens Paul , Gybels Jan
Published: June 2009

✓ The authors discuss the advantages and disadvantages of the use of magnetic resonance (MR) angiography images in stereotactic neurosurgery. Current computer programs designed to assist the neurosurgeon in the planning of stereotactic neurosurgical interventions use intraarterial digital subtraction angiography images to visualize the blood vessels. Magnetic resonance angiography is a recent technique with a number of advantages over the digital subtraction method: it is less invasive and less prone to complications; it provides truly three-dimensional data sets that can be viewed from any direction; and it can visualize both stationary and flowing tissues with the same imaging device and localizer frame. Although digital subtraction images are still superior in contrast and vascular detail, state-of-the-art high-resolution MR angiography sequences provide sufficient vascular detail for planning surgery. Contrast-enhanced MR angiography images were acquired using adapted gradient-echo sequences to compensate for flow-induced distortions; postacquisition distortion correction was not necessary. Five methods to integrate and inspect a possible trajectory in the MR angiography data are discussed. Initial clinical experience with eight patients led to the conclusion that MR angiography is a valuable imaging modality that can be integrated reliably into a stereotactic neurosurgery planning procedure.
Neoplastic and pharmacological influence on the permeability of an in vitro blood-brain barrier
Authors: Grabb Paul A. , Gilbert Mark R.
Published: June 2009

✓ The authors investigated the effects of glioma cells and pharmacological agents on the permeability of an in vitro blood-brain barrier (BBB) to determine the following: 1) whether malignant glia increase endothelial cell permeability; 2) how glucocorticoids affect endothelial cell permeability in the presence and absence of malignant glia; and 3) whether inhibiting phospholipase A2, the enzyme that releases arachidonic acid from membrane phospholipids, would reduce any malignant glioma—induced increase in endothelial cell permeability.

Primary cultures of rat brain capillary endothelium were grown on porous membranes; below the membrane, C6, 9L rat glioma, T98G human glioblastoma, or no cells (control) were cocultured. Dexamethasone (0.1 µM), bromophenacyl bromide (1.0 µM), a phospholipase A2 inhibitor, or nothing was added to culture media 72 hours prior to assaying the rat brain capillary endothelium permeability. Permeability was measured as the flux of radiolabeled sucrose across the rat brain capillary endothelium monolayer and then calculated as an effective permeability coefficient (Pe). When neither dexamethasone nor bromophenacyl bromide was present, C6 cells reduced the Pe significantly (p < 0.05), whereas 9L and T98G cells increased Pe significantly (p < 0.05) relative to rat brain capillary endothelium only (control). Dexamethasone reduced Pe significantly for all cell preparations (p < 0.05). The 9L and T98G cell preparations coincubated with dexamethasone had the lowest Pe of all cell preparations. The Pe was not affected in any cell preparation by coincubation with bromophenacyl bromide (p > 0.45).

These in vitro BBB experiments showed that: 1) malignant glia, such as 9L and T98G cells, increase Pe whereas C6 cells probably provide an astrocytic influence by reducing Pe; 2) dexamethasone provided significant BBB “tightening” effects both in the presence and absence of glioma cells; 3) the in vivo BBB is actively made more permeable by malignant glia and not simply because of a lack of astrocytic induction; 4) tumor or endothelial phospholipase A2 activity is probably not responsible for glioma-induced increased in BBB permeability; and 5) this model is useful for testing potential agents for BBB protection and for studying the pathophysiology of tumor-induced BBB disruption.
Thoracic flexion myelopathy
Authors: Mii Kimihiko , Shimizu Satoru , Tanaka Chihiko , Matsumori Kuniaki , Hasegawa Kazuko , Mizoi Yoshikazu
Published: June 2009

✓ A case of thoracic flexion myelopathy is reported in a 36-year-old man. The patient had a history of gradually progressing transverse thoracic myelopathy. Conventional myelography in the neutral position failed to reveal cord compression; however, a severe block of the dye column was evident on studies in the flexed position. Excellent recovery from this condition was obtained with posterolateral fusion of the thoracic spine in the neutral position.
Bilateral arachnoid cysts of the sylvian region in female siblings with glutaric aciduria type I
Authors: Jamjoom Zain Alabedeen B. , Okamoto Emi , Jamjoom Abdul-Hakim B. , Al-Hajery Osama , Abu-Melha Abdullah
Published: June 2009

✓ Two sisters, aged 6 and 2 1/2 years, presented with macrocephaly and delayed motor development and were found on computerized tomography to have bilateral arachnoid cysts of the sylvian region. Cystoperitoneal shunting of the larger cysts resulted in considerable neurological improvement in both children. Subsequent screening of the patients' urine for organic acids showed that the two sisters were suffering from glutaric aciduria type I (GA-I). To the best of the authors' knowledge, this is the first report to provide clear radiological and surgical evidence of the association between GA-I and bilateral arachnoid cysts of the sylvian region. The role of the shunting procedure used in these cases is discussed.
Surgical management of spinal epidural hematoma: relationship between surgical timing and neurological outcome
Authors: Lawton Michael T. , Porter Randall W. , Heiserman Joseph E. , Jacobowitz Ronald , Sonntag Volker K. H. , Dickman Curtis A.
Published: June 2009

✓ Thirty patients were treated surgically for spinal epidural hematoma (SEH). Twelve of these cases resulted from spinal surgery, seven from epidural catheters, four from vascular lesions, three from anticoagulation medications, two from trauma, and two from spontaneous causes. Pain was the predominant initial symptom, and all patients developed neurological deficits. Eight patients had complete motor and sensory loss (Frankel Grade A); six had complete motor loss but some sensation preserved (Frankel Grade B); and 16 had incomplete loss of motor function (10 patients Frankel Grade C and six patients Frankel Grade D). The average interval from onset of initial symptom to maximum neurological deficit was 13 hours, and the average interval from onset of symptom to surgery was 23 hours. Surgical evacuation of the hematoma was performed in all patients; 26 of these improved; four remained unchanged, and no patients worsened (mean follow up 11 months). Complete recovery (Frankel Grade E) was observed in 43% of the patients and functional recovery (Frankel Grades D or E) was observed in 87%. One postoperative death occurred from a pulmonary embolus (surgical mortality 3%). Preoperative neurological status correlated with outcome; 83% of Frankel Grade D patients recovered completely compared to 25% of Frankel Grade A patients. The rapidity of surgical intervention also correlated with outcome; greater neurological recovery occurred as the interval from symptom onset to surgery decreased. Patients taken to surgery within 12 hours had better neurological outcomes than patients with identical preoperative Frankel grades whose surgery was delayed beyond 12 hours. This large series of SEH demonstrates that rapid diagnosis and emergency surgical treatment maximize neurological recovery. However, patients with complete neurological lesions or long-standing compression can improve substantially with surgery.
Long-term follow up of 57 patients undergoing automated percutaneous discectomy
Authors: Shapiro Scott
Published: June 2009

✓ Automated percutaneous discectomy has been performed in 57 patients at the author's institution since 1989, representing 4% of all lumbar spine surgeries. All 57 patients had unilateral sciatica. There were 33 women and 24 men ranging from 24 to 49 years of age, with a mean age of 45 years. All patients underwent computerized tomography (CT) in the prone position and CT and magnetic resonance imaging in the supine position. Diffuse versus eccentric disc bulging was determined for each patient. Four patients underwent surgery at the L3–4 level, four at L5–S1, and 49 at L4–5. One L5–S1 case could not be cannulated and surgery was aborted. There have been no complications related to surgery. Fifty patients (88%) stated they had reduced sciatica in the first 2 postoperative weeks. Forty (70%) had reduced sciatica 2 months postoperatively. The mean follow-up period was 27 months (range 6 to 45 months), with no patient lost to follow up. At their last follow-up examination, 33 patients (58%) showed improvement in their sciatica but only three (5%) were completely pain free. Of the 17 recurrences of sciatica, 11 patients have undergone microdiscectomy, with eight showing improvement. Chi-square analysis demonstrated a significantly better chance of improvement in patients with discs bulging eccentrically to the side of sciatica (p < 0.05) compared to patients with diffusely bulging discs. Automated percutaneous discectomy is safe and in selected patients can reduce sciatica, but only completely eliminated sciatica in 5% of patients with a follow-up period of 2.5 years.
Early treatment of subarachnoid hemorrhage after preventing rerupture of an aneurysm
Authors: Kinugasa Kazushi , Kamata Ichiro , Hirotsune Nobuyuki , Tokunaga Koji , Sugiu Kenji , Handa Akira , Nakashima Hiroyuki , Ohmoto Takashi , Mandai Shinya , Matsumoto Yuzo
Published: June 2009

✓ Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had diffuse or localized thick subarachnoid blood clots, two had diffuse thin clots, and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome.
A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model
Authors: Ceberg Crister P. , Brun Arne , Kahl Stephen B. , Koo Myoung Seo , Persson Bertil R. R. , Salford Leif G.
Published: June 2009

✓ Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain.

The animals were infused intravenously with either BSH (25 µg or 175 µg of boron per gram of body weight) or BOPP (12 µg of boron per gram body weight). For the low dose of BSH, the maximum tumor—boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor—boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.