bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme
Authors: Darakchiev Borimir J. , Albright Robert E. , Breneman John C. , Warnick Ronald E.
Published: February 2008

Object

Effective treatment options are limited for patients with recurrent glioblastoma multiforme (GBM), and survival is usually <1 year. Novel treatment approaches are needed. Localized adjunct treatment with carmustine (BCNU) wafers or permanent, low-activity 125I seed implants has been shown to be effective for GBM. This study assessed the efficacy and safety of these therapies in combination following tumor resection.

Methods

Thirty-four patients with recurrent GBM were treated with maximal tumor resection followed by implantation of BCNU wafers and permanent 125I seeds into the tumor cavity. Patients were followed up with clinical evaluations and magnetic resonance imaging studies once every 3 months. Survival and progression-free survival (PFS) were evaluated.

Results

During follow-up, local disease progression was observed in 27 patients, and 23 of them died. The median survival period was 69 weeks, and the median PFS was 47 weeks. The 12-month survival and PFS rates were 66 and 32%, respectively. Baseline factors associated with prolonged survival included Karnofsky Performance Scale score ≥ 70, 125I seed activity ≥ 0.8 mCi/cm3 of tumor cavity, and age < 60 years. Brain necrosis developed in 8 patients (24%) and was successfully treated with surgery or hyperbaric oxygen therapy.

Conclusions

The use of adjunct therapy combining BCNU wafers and permanent 125I seeds resulted in survival that compares favorably with data from similar studies performed in patients with recurrent GBM. The incidence of brain necrosis appeared to be higher than that expected with either treatment alone, although the necrosis was manageable and did not affect survival. This novel approach warrants further investigation in recurrent and newly diagnosed GBM.
Cranial melioidosis presenting as a mass lesion or osteomyelitis
Authors: Kumar G. Samson Sujit , Raj Promila Mohan , Chacko Geeta , Lalitha Mukkai K. , Chacko Ari. G. , Rajshekhar Vedantam
Published: February 2008

Object

Melioidosis is caused by Burkholderia pseudomallei and causes multiple abscesses in different organs of the body. Cranial melioidosis, although uncommon, is sometimes confused with tuberculosis and is therefore underecognized. The authors report on 6 cases of cranial infections caused by Burkholderia pseudomalleii, presenting as mass lesions or cranial osteomyelitis, and review the literature.

Methods

The authors performed a retrospective review of the records of patients with cranial melioidosis treated at their institution between 1998 and 2005 to determine the presentation, management, and outcome of patients with this infection.

Results

Of the 6 patients diagnosed with cranial melioidosis during this period, 4 had brain abscesses and 2 had cranial osteomyelitis. All patients were treated surgically, and a diagnosis was made on the basis of histopathological studies. All patients were started on antibiotic therapy following surgery and this was continued for 6 months. One patient died soon after stereotactic aspiration of a brain abscess, and the other 5 patients had good outcomes.

Conclusions

Cranial melioidosis is probably more prevalent than has been previously reported. A high index of suspicion, early diagnosis, initiation of appropriate antibiotic therapy and treatment for an adequate period are essential for assuring good outcome in patients with cranial melioidosis. The authors recommend surgery followed by intravenous ceftazidime treatment for 6 weeks and oral cotrimoxazole for 6 months thereafter in patients with cranial melioidosis.
Robotic catheter ventriculostomy: feasibility, efficacy, and implications
Authors: Lollis S. Scott , Roberts David W.
Published: February 2008

Object

Robotic applications hold great promise for improving clinical outcomes and reducing complications of surgery. To date, however, there have been few widespread applications of robotic technology in neurosurgery. The authors hypothesized that image-guided robotic placement of a ventriculostomy catheter is safe, highly accurate, and highly reproducible.

Methods

Sixteen patients requiring catheter ventriculostomy for ventriculoperitoneal (VP) shunt or reservoir placement were included in this retrospective study. All patients underwent image-guided robotic placement of a ventricular catheter, using a preoperatively defined trajectory.

Results

All catheters were placed successfully in a single pass. There were no catheter-related hemorrhages and no injuries to adjacent neural structures. The mean distance of the catheter tip from the target was 1.5 mm. The mean operative times were 112 minutes for VP shunt placement and 42.3 minutes for reservoir placement. The mean operative times decreased over the course of the study by 49% for VP shunts and by 19% for reservoir placement.

Conclusions

The robotic placement of a ventriculostomy catheter using a preplanned trajectory is safe, highly accurate, and highly reliable. This makes single-pass ventriculostomy possible in all patients, even in those with very small ventricles, and may permit catheter-based therapies in patients who would otherwise be deemed poor surgical candidates because of ventricle size. Robotic placement also permits careful preoperative study and optimization of the catheter trajectory, which may help minimize the risks to bridging veins and sulcal vessels.
State and trait anxiety and depression in patients with primary brain tumors before and after surgery: 1-year longitudinal study
Authors: D'Angelo Cristina , Mirijello Antonio , Leggio Lorenzo , Ferrulli Anna , Carotenuto Vincenzo , Icolaro Nadia , Miceli Antonio , D'Angelo Vincenzo , Gasbarrini Giovanni , Addolorato Giovanni
Published: February 2008

Object

The aim in this study was to assess the state and trait types of anxiety as well as current depression before and after surgery in patients affected by brain tumors. The relationships between these affective disorders and the patient's sex, tumor histology, and laterality of the tumor were also evaluated.

Methods

A total of 72 patients affected by a primary brain tumor were enrolled in the study. Histological grades were assigned according to the World Health Organization classification. State and trait anxiety were assessed using the State and Trait Anxiety Inventory; current depression was assessed using the Zung Self-Rating Depression Scale. Cognitive impairment was assessed using the 10-item Short Portable Mental Status Questionnaire. Psychometric evaluation was assessed before surgery and at 1, 3, 6, and 12 months after surgery.

Results

Before brain surgery, 62.5% of patients showed state anxiety, 50% of patients showed trait anxiety, and 9.7% of patients showed current depression. During the follow-up period there was no significant variation in the percentage of patients with state anxiety (p = 0.416) and trait anxiety (p = 0.7), whereas a significant increase in the percentage of those with current depression was found (p < 0.0001), in particular at 1 month (p = 0.002) and 3 months (p = 0.039) after surgical treatment. The tumor's laterality and histology showed no correlation with psychometric variables, whereas a relationship between the presence of trait anxiety at the enrollment and current depression after surgery (p < 0.0001) was found.

Conclusions

Patients affected by brain tumors frequently experience affective disorders. After brain surgery, a depressive state can develop. The psychometric assessment could be useful in these patients for quick recognition of psychological disorders.
Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial
Authors: Kemler Marius A. , de Vet Henrica C. W. , Barendse Gerard A. M. , van den Wildenberg Frans A. J. M. , van Kleef Maarten
Published: February 2008

Object

Chronic complex regional pain syndrome–Type I (CRPS-I) is a painful, disabling disorder for which no treatment with proven effect is available. In the present randomized controlled trial, the authors assessed the effectiveness of spinal cord stimulation (SCS) in reducing pain due to CRPS-I at the 5-year follow-up.

Methods

The authors performed a randomized trial in a 2:1 ratio in which 36 patients with CRPS-I were allocated to receive SCS and physical therapy (PT) and 18 patients to receive PT alone. Twenty-four patients who received SCS+PT also underwent placement of a permanent spinal cord stimulator after successful test stimulation; the remaining 12 patients did not receive a permanent stimulator. The authors assessed pain intensity, global perceived effect, treatment satisfaction, and health-related quality of life. Patients were examined before randomization, before implantation, and every year until 5 years thereafter. Ten patients were excluded from the final analysis.

Results

At 5 years posttreatment, SCS+PT produced results similar to those following PT for pain relief and all other measured variables. In a subgroup analysis, the results with regard to global perceived effect (p = 0.02) and pain relief (p = 0.06) in 20 patients with an implant exceeded those in 13 patients who received PT.

Conclusions

Despite the diminishing effectiveness of SCS over time, 95% of patients with an implant would repeat the treatment for the same result.
Increased expression of the glioma-associated antigen ARF4L after loss of the tumor suppressor PTEN
Authors: Chi John H. , Panner Amith , Cachola Kristine , Crane Courtney A. , Murray Joseph , Pieper Russell O. , James C. David , Parsa Andrew T.
Published: February 2008

Object

Despite recent advances in cancer immunotherapy, cellular mechanisms controlling expression of tumor-associated antigens are poorly understood. Mutations in cancer cells, such as loss of PTEN, may increase expression of tumor-associated antigens. The authors investigated the relationship between PTEN status and the expression of a glioma-associated antigen, adenosine diphosphate–ribosylation factor 4–like (ARF4L) protein.

Methods

Human glioma cell lines with confirmed PTEN status were examined by Northern blot analysis and quantitative polymerase chain reaction. Western blot analysis was used to measure ARF4L protein levels across multiple cell lines.

Results

The loss of PTEN was shown to lead to increased levels of ARF4L protein but no change in transcript levels. Cell lines with serial mutations, including activation of Ras and Akt pathways, also demonstrated increased levels of ARF4L protein, which decreased after treatment with rapamycin. The ARF4L transcript preferentially localized to the polysomal compartment after PTEN loss in glioma or activation of Akt in human astrocytes.

Conclusions

Expression of ARF4L is controlled by the activated Akt/mTOR pathway, which is a downstream effect of the loss of PTEN function. Mutations leading to oncogenesis may impact the regulation and expression of tumor specific antigens. Screening of mutation status in glioma may be helpful in selecting patients for immunotherapy trials in the future.
Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase–1 expression in murine microglia by glioma-derived soluble factors
Authors: Nakano Yoshiteru , Kuroda Etsushi , Kito Tomohiro , Uematsu Satoshi , Akira Shizuo , Yokota Akira , Nishizawa Shigeru , Yamashita Uki
Published: February 2008

Object

Microglia are one of the members of monocyte/macrophage lineage in the central nervous system (CNS) and exist as ramified microglia in a normal resting state, but they are activated by various stimuli, such as tumors. Activated microglia induce immune responses in the CNS, but the precise functions of microglia in glioma microenvironments are not clear. It has been reported that glioma cells produce prostaglandin (PG)E2, which promotes the growth of tumor cells and possesses immunosuppressive activity. The authors previously reported that PGE2 production by peritoneal macrophages was enhanced by glioma-derived soluble factors, which induce an immunosuppressive state. In this study, they investigated PGE2 production by microglia treated with glioma cells and assessed the role of microglia in glioma microenvironments in the mouse.

Methods

Microglia and peritoneal macrophages were cultured in vitro with or without lipopolysaccharide, and tumor necrosis factor (TNF) and PGE2 in the culture supernatant were measured using L929 bioassay and enzyme immunoassay. The expression of mRNA was measured using reverse transcriptase polymerase chain reaction, and the protein expression was assayed with Western blotting. In some experiments glioma cells and conditioned glioma medium were added to the microglia cultures.

Results

Glioma cells studied in this report did not produce a significant amount of PGE2. However, the coculture of microglia with glioma cells or conditioned glioma medium led to the production of a large amount of PGE2. The enhancement of PGE2 production by microglia was more significant than that by peritoneal macrophages. The expression of cyclooxygenase (COX)–2 and particularly the expression of microsomal PGE synthase (mPGES)–1 (a terminal enzyme of the arachidonate cascade) in microglia were enhanced by conditioned glioma medium. The enhancement of mPGES-1 expression in microglia was more significant than that in peritoneal macrophages. The production of TNF was suppressed when culturing microglia with conditioned glioma medium, but this suppression was abrogated by the addition of a COX inhibitor (NS-398) and a PGE2 receptor (EP4) antagonist. Furthermore, TNF production was not suppressed in microglia from mPGES-1–deficient mice.

Conclusions

These results indicate that PGE2 production by microglia is enhanced by conditioned glioma medium, which induces an immunosuppressive state in the CNS. Therefore, the manipulation of microglia, from the standpoint of PGE2, provides investigators with an important strategy to induce an effective antiglioma immune response.
In vivo tracking of superparamagnetic iron oxide nanoparticle–labeled mesenchymal stem cell tropism to malignant gliomas using magnetic resonance imaging
Authors: Wu Xing , Hu Jin , Zhou Liangfu , Mao Ying , Yang Bojie , Gao Liang , Xie Rong , Xu Feng , Zhang Dong , Liu Jun , Zhu Jianhong
Published: February 2008

Object

Mesenchymal stem cells (MSCs) have been shown to migrate toward tumors, but their distribution pattern in gliomas has not been completely portrayed. The primary purpose of the study was to assay the tropism capacity of MSCs to gliomas, to delineate the pattern of MSC distribution in gliomas after systemic injection, and to track the migration and incorporation of magnetically labeled MSCs using 1.5-T magnetic resonance (MR) imaging.

Methods

The MSCs from Fischer 344 rats were colabeled with superparamagnetic iron oxide nanoparticles (SPIO) and enhanced green fluorescent protein (EGFP). The tropism capacity of MSCs was quantitatively assayed in vitro using the Transwell system. To track the migration of MSCs in vivo, MR imaging was performed both 7 and 14 days after systemic administration of labeled MSCs. After MR imaging, the distribution patterns of MSCs in rats with gliomas were examined using Prussian blue and fluorescence staining.

Results

The in vitro study showed that MSCs possessed significantly greater migratory capacity than fibroblast cells (p < 0.001) and that lysis of F98 glioma cells and cultured F98 cells showed a greater capacity to induce migration of cells than other stimuli (p < 0.05). Seven days after MSC transplantation, the SPIO–EGFP colabeled cells were distributed throughout the tumor, where a well-defined dark hypointense region was represented on gradient echo sequences. After 14 days, most of the colabeled MSCs were found at the border between the tumor and normal parenchyma, which was represented on gradient echo sequences as diluted amorphous dark areas at the edge of the tumors.

Conclusions

This study demonstrated that systemically transplanted MSCs migrate toward gliomas with high specificity in a temporal–spatial pattern, which can be tracked using MR imaging.
Utility of EGFR and PTEN numerical aberrations in the evaluation of diffusely infiltrating astrocytomas
Authors: Mott Ryan T. , Turner Kristi C. , Bigner Darell D. , McLendon Roger E.
Published: February 2008

Object

DIFFUSELY infiltrating astrocytomas are the most common primary brain tumors. As a group, they demonstrate an inherent tendency toward malignant progression. Histological grading using the guidelines of the World Health Organization (WHO) remains the gold standard for predicting the biological behavior of these tumors. Although useful, this grading system is often limited due to small sample sizes and the subjectivity in interpretation. Given the important roles for EGFR and PTEN in the malignant progression of astrocytomas, the authors hypothesized that the fraction of tumor cells with aberrations in these genetic loci would correlate with the histological grade.

Methods

The authors evaluated 217 consecutive diffusely infiltrating astrocytomas that were graded using the WHO guidelines, including 16 diffuse astrocytomas (WHO Grade II), 72 anaplastic astrocytomas ([AAs] WHO Grade III), and 129 glioblastomas multiforme ([GBMs] WHO Grade IV). Cases were evaluated quantitatively using dual-color fluorescence in situ hybridization with probes for the EGFR and PTEN loci and the centromeres of chromosomes 7 and 10.

Results

The population of tumor cells with polysomy of chromosome 7 and the EGFR locus and monosomy of chromosome 10 and the PTEN locus correlated significantly with histological grade. In particular, high-grade astrocytomas (that is, AAs and GBMs) had elevated fractions of tumor cells with polysomy of chromosome 7 and the EGFR locus and monosomy of chromosome 10 and the PTEN locus. Using these findings, the authors generated a mathematical model capable of subcategorizing high-grade astrocytomas. The successful model incorporated only the percentage of tumor cells with polysomy of EGFR and monosomy of PTEN, as well as patient age. The predictions of this model correlated with survival in a manner similar to histopathological grading.

Conclusions

The findings presented in this study emphasize the utility of combining histological interpretation and molecular testing in the evaluation of infiltrating astrocytomas. These results underscore the utility of building a grading framework that combines histopathological and molecular analysis.
Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey
Authors: Laćan Goran , De Salles Antonio A. F. , Gorgulho Alessandra A. , Krahl Scott E. , Frighetto Leonardo , Behnke Eric J. , Melega William P.
Published: February 2008

Object

Deep brain stimulation (DBS) has become an effective therapy for an increasing number of brain disorders. Recently demonstrated DBS of the posterior hypothalamus as a safe treatment for chronic intractable cluster headaches has drawn attention to this target, which is involved in the regulation of diverse autonomic functions and feeding behavior through complex integrative mechanisms. In this study, the authors assessed the feasibility of ventromedial hypothalamus (VMH) DBS in freely moving vervet monkeys to modulate food intake as a model for the potential treatment of eating disorders.

Methods

Deep brain stimulation electrodes were bilaterally implanted into the VMH of 2 adult male vervet monkeys by using the stereotactic techniques utilized in DBS in humans. Stimulators were implanted subcutaneously on the upper back, allowing ready access to program stimulation parameters while the animal remained conscious and freely moving. In anesthetized animals, intraoperatively and 6–10 weeks postsurgery, VMH DBS parameters were selected according to minimal cardiovascular and autonomic nervous system responses. Thereafter, conscious animals were subjected to 2 cycles of VMH DBS for periods of 8 and 3 days, and food intake and behavior were monitored. Animals were then killed for histological verification of probe placement.

Results

During VMH DBS, total food consumption increased. The 3-month bilateral implant of electrodes and subsequent periods of high-frequency VMH stimulation did not result in significant adverse behavioral effects.

Conclusions

This is the first study in which techniques of hypothalamic DBS in humans have been applied in freely moving nonhuman primates. Future studies can now be conducted to determine whether VMH DBS can change hypothalamic responsivity to endocrine signals associated with adiposity for long-term modulation of food intake.
Bilateral temporal bone xanthoma
Authors: Muthusamy Kalai A. , Azmi Khairul , Narayanan Prepageran , Rajagopalan Raman , Rahman Nazarina Abdul , Waran Vicknes
Published: February 2008

✓Xanthoma formation is frequently seen over the subcutaneous tissue of extensor surfaces and tendons that have received minor trauma or friction in patients with hypercholesterolemia. However, temporal bone xanthomas with intracranial extension are uncommon. To the best of the authors' knowledge, this is the second report in the literature in which bilateral extension of a xanthoma is described. Xanthomas of the temporal bone are benign lesions, and complete or even partial removal is effective. The predisposing cause of the lesion should also be treated.
Inflammatory pseudotumor of the choroid plexus
Authors: Miyahara Kosuke , Fujitsu Kazuhiko , Yagishita Saburo , Takemoto Yasunori , Ichikawa Teruo , Matsunaga Shigeo , Takeda Yukihiro , Niino Hitoshi , Shiina Takeki
Published: February 2008

✓The authors report a case of inflammatory pseudotumor that developed in the choroid plexus of the lateral ventricle. The patient was a 73-year-old man who had undergone surgery for rectal cancer at another hospital 5 years earlier. He was referred to the authors' department, with his chief symptoms consisting of disorientation, right hemiparesis, and gait disorder that had gradually developed during the preceding month. On computed tomography and magnetic resonance imaging, a well-demarcated and homogeneously contrasted tumorous lesion was noted in the region from the trigone to the medial wall of the inferior horn of the left lateral ventricle. Expansion of the inferior horn was also evident. Intraoperative findings showed that the tumor originated from the choroid plexus of the lateral ventricle, and the histopathological diagnosis was inflammatory pseudotumor. There are only 4 previously reported cases of inflammatory pseudotumor that developed in the choroid plexus; the authors review the literature and discuss the clinicopathological characteristics of the condition.
Severe brain edema caused by a meningioma obstructing cerebral venous outflow and treated with venous sinus stenting
Authors: Higgins J. Nicholas P. , Burnet Neil G. , Schwindack Christian F. , Waters Alan
Published: February 2008

✓ Peritumoral edema is a common feature of cerebral meningiomas, but venous outflow obstruction is not normally considered as a cause even when a tumor involves the venous sinuses. The authors describe a patient with a ventricu-loperitoneal shunt in situ, who had undergone several debulking operations and conventional radiotherapy and in whom had developed progressive life-threatening edema from a tentorial meningioma. Radiological studies showed occlusion of the straight sinus and stenosis of the sagittal sinus at the confluence of sinuses. The sagittal sinus was stented, and thereafter the patient made an almost complete symptomatic recovery and returned to work. This case shows that progressive edema in patients with meningioma is not necessarily caused by radiotherapy or tumor enlargement into the brain and that in venous outflow obstruction, addressing the obstructive lesion directly can improve the palliation afforded by a shunt.
Patton: death of a soldier
Authors: Rovit Richard L. , Simon Arlene Stolper , Couldwell William T.
Published: February 2008

✓ General George S. Patton Jr. died as the result of quadriplegia sustained in a car crash in Germany in 1945. His x-ray films revealed a fractured C-3 vertebra and a posterior dislocation of C-4 on C-5. The likely cause of death was a pulmonary embolus. Details of his medical treatment are reviewed and compared with therapies that a patient with a similar injury would receive today.
Cortical language localization in left, dominant hemisphere
Authors: Ojemann George , Ojemann Jeff , Lettich E. , Berger M.
Published: February 2008

✓ The localization of cortical sites essential for language was assessed by stimulation mapping in the left, dominant hemispheres of 117 patients. Sites were related to language when stimulation at a current below the threshold for afterdischarge evoked repeated statistically significant errors in object naming. The language center was highly localized in many patients to form several mosaics of 1 to 2 sq cm, usually one in the frontal and one or more in the temporoparietal lobe. The area of individual mosaics, and the total area related to language was usually much smaller than the traditional Broca-Wernicke areas. There was substantial individual variability in the exact location of language function, some of which correlated with the patient's sex and verbal intelligence. These features were present for patients as young as 4 years and as old as 80 years, and for those with lesions acquired in early life or adulthood. These findings indicate a need for revision of the classical model of language localization. The combination of discrete localization in individual patients but substantial individual variability between patients also has major clinical implications for cortical resections of the dominant hemisphere, for it means that language cannot be reliably localized on anatomic criteria alone. A maximal resection with minimal risk of postoperative aphasia requires individual localization of language with a technique like stimulation mapping.
Progressive and symmetric supraorbital hyperostosis with bony and soft tissue overgrowth in an Ethiopian female: A newly recognized overgrowth syndrome?
Authors: Adam Margaret P. , Kobori Joyce A. , Cusmano‐Ozog Kristina , Chen Kelly M. , Hoyme H. Eugene
Published: February 2008

We report on an Ethiopian female with generalized overgrowth of postnatal onset accompanied by progressive and symmetric overgrowth of skeletal and soft tissues. Her phenotype consisted of progressive and symmetric overgrowth of the supraorbital ridges, glabella, occiput, cervical spine, and distal phalanges of all extremities, but particularly the 3rd and 4th digits. She also has overgrowth of soft tissues of the posterior neck (thought to be fatty in origin), alveolar hyperplasia, and overgrowth of the skin comprising the areola and umbilicus. Other clinical findings included obstructive sleep apnea and normal intelligence. A genetic workup of extended banding chromosome analysis and chromosomal microarray were normal, as were PTEN and FNLA mutation analyses. Histologic examination of the excised supraorbital ridges demonstrated normal bone. However, the bone began to regrow in a symmetric fashion within 3 months of removal. This patient's phenotype is at variance with any known overgrowth syndrome. © 2008 Wiley‐Liss, Inc.
The first study of the effect of surfmer backbone structure on the stability and the course of emulsion polymerization of methyl methacrylate and butyl acrylate monomers
Authors: Shaffei K. A.
Published: February 2008

This is the first study of the effect of structure of the surfmer on the stability, morphology, and kinetics of the emulsion polymerization of butyl acrylate (BuA) and methyl methacrylate (MMA). Poly(ethylene glycol) behenyl ether methacrylate (PEGBEMA) was used as surfmer in the emulsion polymerization magnified imageof BuA and MMA and compared with the same type surfmer with different backbone structure (with four bulky phenyl groups in the backbone of the surfmer) poly(ethylene glycol) 2,4,6‐tris (1‐phenylethyl) phenyl ether methacrylate. magnified image It was found that the straight chain surfmer produces less stability, lower order reaction less particles size (Dmax) greater number of polymer particles Nt, worse morphology Dw/Dn, than the bulky surfmer. The order of polymerization reaction of BuA with respect to PEGBEMA was 0.8 compared with 2.6 in case of using PEGTPMA. The surface charge density was dramatically changed when using PEGBEMA from 39.8 to 204 μC in case of PEGTPMA at the same conditions of surfmer concentration, temperature, and other parameters. The Dv was found to be 897 nm for particles prepared in the presence of PEGTPMA surfmer while it was 159 nm for particles prepared in the presence of PEGBEMA at the same surfmer concentrations and other experimental conditions. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Control of vulcanizing/devulcanizing behavior of diphenyl disulfide with microwaves as the heating source
Authors: Vega B. , Montero L. , Lincoln S. , Agulló N. , Borrós S.
Published: February 2008

Diphenyl disulfide is a common agent used in the devulcanization of sulfur‐vulcanized goods. Its activity has been tested both in real rubber samples and in model molecules but, to the best of our knowledge, always under normal heating conditions. Moreover, there is a lack of information about how the vulcanizing potential of the molecule can affect the devulcanization yield. In this study, the diphenyl disulfide behavior has been studied in model compound vulcanization, with squalene used as a model molecule of natural rubber. Microwaves have been used as a heating source, and the vulcanization/devulcanization behavior of the molecules has been characterized. The results have shown that it is possible to tailor the diphenyl disulfide activity by controlling the reaction temperature and also through microwave power control. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Investigation of the surface properties of polymeric soaps obtained by ring‐opening polymerization of epoxidized soybean oil
Authors: Biresaw G. , Liu Z. S. , Erhan S. Z.
Published: February 2008

Epoxidized soybean oil (ESO) was converted to a polysoap (PESO) via a two‐step synthetic procedure of catalytic ring‐opening polymerization, followed by hydrolysis (HPESO) with a base. Various molecular weights of PESO and HPESO were prepared by varying the reaction temperature and/or catalyst concentration. In addition, the counter ion chemistry was varied by changing the base used for saponification. The PESO and HPESO products were carefully characterized and identified using a combination of FTIR, 1H‐NMR, solid state 13C‐NMR, and GPC. The effect of HPESO polysoaps on the surface tension of water and the interfacial tension of water‐hexadecane was investigated as a function of HPESO concentration, molecular weight, and counter ion chemistry. HPESO polysoaps were effective at lowering the surface tension of water and the interfacial tension of water‐hexadecane and displayed minimum values in the range of 20–24 and 12–17 dyn/cm, respectively, at concentration of 200–250 μM. Water‐hexadecane interfacial tension was also calculated from measured surface tension data using the Antonoff, harmonic mean (HM), and geometric mean (GM) methods. Measured values agreed well with those calculated using the HM and GM methods, but not the Antonoff method. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Preparation and morphological evolution of heterophasic PP‐EP/EVA/organoclay nanocomposites: Effect of the nanoclay organic modifier
Authors: Valera‐Zaragoza M. , Ramírez‐Vargas E. , Medellín‐Rodríguez F. J.
Published: February 2008

A study is presented on the morphological effects caused by the nanoclay organic modifier and the nanoclay concentration. This was made under previously determined compatibility conditions of heterophasic polypropylene copolymers (PP‐EP)/poly(ethylene vinyl acetate) (EVA)/organoclay nanocomposites. The nanocomposites were prepared using the fluidity of the EVA phase to disperse the nanoclay platelets. Therefore, no additional compatibilizer was used to achieve the clay dispersion. Two organoclays were used with different characteristics and polarity of the substituent groups. Transmission electron microscopy and X‐ray diffraction results first indicated that two hydrogenated tallow modifiers are more effective than one to enhance nanoclay exfoliation. Thermogravimetric studies indicated a low probability of thermal degradation of the nanoclay modifiers and as a consequence of their effect on the layer–layer exfoliation. Molecular simulations were made with the purpose to study additional factors affecting exfoliation. The introduction of nanoclay, within the compatibility conditions of the PP‐EP/EVA system, was also studied. It was determined that the system preserved its original morphology and that the silicate layers were hosted by the EVA domains. The crystallization characteristics of the PP‐EP/EVA mixtures indicated a gradual evolution of the overall crystalline structures depending on the EVA content. In the case of the ternary nanocomposites PP‐EP/EVA/nanoclay, the β crystalline structure was partially formed, although it decreased with increasing nanoclay content. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Oligomeric Alkoxysilanes with Cagelike Hybrids as Cores: Designed Precursors of Nanohybrid Materials
Authors: Kuge Hideki , Hagiwara Yoshiaki , Shimojima Atsushi , Kuroda Kazuyuki
Published: February 2008

Well‐defined alkoxysilane oligomers containing a cagelike carbosiloxane core were synthesized and used as novel building blocks for the formation of siloxane‐based hybrid networks. These oligomers were synthesized from the cagelike trimer derived from bis(triethoxysilyl)methane by silylation with mono‐, di‐, and triethoxychlorosilanes ((EtO)nMe3−nSiCl, n=1, 2, and 3). Hybrid xerogels were prepared by hydrolysis and polycondensation of these oligomers under acidic conditions. The structures of the products varied depending on the number of alkoxy groups (n). When n=2 and 3, microporous xerogels (BET surface areas of 820 and 510 m2 g−1, respectively) were obtained, whereas a nonporous xerogel was obtained when n=1. 29Si NMR spectroscopic analysis suggested that partial rearrangement of the siloxane networks, which accompanied the cleavage of the Si–O–Si linkages, occurred during the polycondensation processes. By using an amphiphilic triblock copolymer surfactant as a structure‐directing agent, hybrid thin films with a 2D hexagonal mesostructure were obtained when n=2 and 3. These results provide important insight into the rational synthesis of molecularly designed hybrid materials by sol–gel chemistry.
Strategies for systems‐level metabolic engineering
Authors: Kim Tae Yong , Sohn Seung Bum , Kim Hyun Uk , Lee Sang Yup
Published: February 2008

Bio‐based production of chemicals, fuels and materials is becoming more and more important due to the increasing environmental problems and sharply increasing oil price. To make these biobased processes economically competitive, the biotechnology industry explores new ways to improve the performance of microbial strains in fermentation processes. In contrast to the random mutagenesis and/or intuitive local metabolic engineering practiced in the past, we are now moving towards global‐scale metabolic engineering, aided by various experimental and computational tools. This has recently led to some remarkable achievements for the overproduction of valueadded products. In this review, we highlight several relevant gene manipulation tools and computational tools using genome‐scale stoichiometric models, and provide useful strategies for successful metabolic engineering along with selected exemplary studies.
Injectable and sustained delivery of human growth hormone using chemically modified Pluronic copolymer hydrogels
Authors: Park Sung Young , Chung Hyun Jung , Lee Yuhan , Park Tae Gwan
Published: February 2008

A new injectable biodegradable hydrogel system with thermosensitive sol‐gel transition behavior was developed. A series of A‐B‐A triblock copolymers consisting of Pluronic copolymer end‐capped with D‐ or L‐lactic acid oligomers (PL‐LAn) with various chain lengths (n = 5,12) was synthesized. It was assumed that a pair of two triblock copolymers with enantiomeric oligolactide chains, when blended in an equimolar mixture, would form more stable, self‐assembled, and stereocomplexed (ST) hydrogels. A series of blend hydrogels encapsulating human growth hormone (hGH) was prepared by varying blend ratios between PL and stereocomplexed PL copolymers. They showed sustained release of hGH via an erosion‐dependent mechanism. The hydrogel with a 5% blending ratio exhibited the most delayed mass erosion as well as sustained protein release patterns in vitro possibly due to the formation of a fish‐net like 3‐D mesh structure. The effect of incubation condition on hGH release and degradation behaviors was also assessed.
Flexible manufacturing cell SCADA system for educational purposes
Authors: Reynard Sarah , Gomis‐Bellmunt Oriol , Sudrià‐Andreu Antoni , Boix‐Aragonès Oriol , Benítez‐Pina Israel
Published: February 2008

This article deals with the development of a Supervisory Control and Data Acquisition SCADA system to be used in a flexible manufacturing cell for educational purposes in different automation engineering fields (SCADA development, PLC programming and industrial communications). When dealing with industrial communications or PLC programming the SCADA is employed as a supervision tool. In the other hand, when teaching SCADA systems the application will be developed by the students and the SCADA presented in this article is employed as a model. The application communicates through Internet with four controllers, by means of an OPC server, visualizes comprehensive information about the elements of the cell, includes the video streaming of an IP camera, and features traceability and report generation capabilities. © 2008 Wiley Periodicals, Inc. Comput Appl Eng Educ 16: 21–30, 2008; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20115
Metal‐Ion‐Dependent Biological Properties of a Chelator‐Derived Somatostatin Analogue for Tumour Targeting
Authors: Heppeler Axel , André João P. , Buschmann Ingeborg , Wang Xuejuan , Reubi Jean‐Claude , Hennig Michael , Kaden Thomas A. , Maecke Helmut R.
Published: February 2008

Somatostatin‐based radioligands have been shown to have sensitive imaging properties for neuroendocrine tumours and their metastases. The potential of [55Co(dotatoc)] (dotatoc =4,7,10‐tricarboxymethyl‐1,4,7,10‐tetraazacyclododecane‐1‐ylacetyl‐D‐Phe‐(Cys‐Tyr‐D‐Trp‐Lys‐Thr‐Cys)‐threoninol (disulfide bond)) as a new radiopharmaceutical agent for PET has been evaluated. 57Co was used as a surrogate of the positron emitter 55Co and the pharmacokinetics of [57Co(dotatoc)] were investigated by using two nude mouse models. The somatostatin receptor subtype (sst1–sst5) affinity profile of [natCo(dotatoc)] on membranes transfected with human somatostatin receptor subtypes was assessed by using autoradiographic methods. These studies revealed that [57Co(dotatoc)] is an sst2‐specific radiopeptide which presents the highest affinity ever found for the sst2 receptor subtype. The rate of internalisation into the AR4‐2J cell line also was the highest found for any somatostatin‐based radiopeptide. Biodistribution studies, performed in nude mice bearing an AR4‐2J tumour or a transfected HEK‐sst2 cell‐based tumour, showed high and specific uptake in the tumour and in other sst‐receptor‐expressing tissues, which reflects the high receptor binding affinity and the high rate of internalisation. The pharmacologic differences between [57Co(dotatoc)] and [67Ga(dotatoc)] are discussed in terms of the structural parameters found for the chelate models [CoII(dota)]2− and [GaIII(dota)]− whose X‐ray structures have been determined. Both chelates show six‐fold coordination in pseudo‐octahedral arrangements.
Testing Electron Transfer within Molecular Associates Built around Anionic C60 and C70 Dendrofullerenes and a Cationic Zinc Porphyrin
Authors: Sarova Ginka H. , Hartnagel Uwe , Balbinot Domenico , Sali Sevda , Jux Norbert , Hirsch Andreas , Guldi Dirk M.
Published: February 2008

Mono‐ and bis‐functionalized C60 and C70 fullerene derivatives (DF, 1–10) that carry one or two oligoanionic dendritic termini in their malonate addends and an oligocationic octapyridinium zinc porphyrin salt (ZnP) were found to self‐assemble in buffered aqueous solution to yield a novel series of 1:1 and/or 1:2 electron transfer hybrid associates. Remarkably high association constants—typically on the order of 108 M−1—were derived that corroborate stable complex formations. A combination of electrostatic and charge‐transfer interactions that are operative between the electron‐accepting DF and the electron‐donating ZnP is considered to contribute to the uniquely high complex stability. First insight into intracomplex excited state interactions came from steady‐state and time‐resolved fluorescence quenching experiments that were performed with the molecular ZnP/DF hybrid associates. Excited state quenching processes are, for example, evident in form of a bi‐exponential fluorescence decay of ZnP—corresponding to a distribution of associated and non‐associated ZnP. Unambiguous evidence for an intracomplex electron transfer quenching, namely, formation of ZnP.+/C60.− and ZnP.+/C70.− radical ion pairs, was gathered in time‐resolved transient absorption measurements. Lifetimes of these radical ion‐pairs range from nanoseconds to a few microseconds.
An Enantioselective Biginelli Reaction Catalyzed by a Simple Chiral Secondary Amine and Achiral Brønsted Acid by a Dual‐Activation Route
Authors: Xin Junguo , Chang Lu , Hou Zongrui , Shang Deju , Liu Xiaohua , Feng Xiaoming
Published: February 2008

An enantioselective Biginelli reaction that proceeds by a dual‐activation route has been developed by using a combined catalyst of a readily available trans‐4‐hydroxyproline‐derived secondary amine and a Brønsted acid. Aromatic, heteroaromatic, and fused‐ring aldehydes were found to be suitable substrates for this multicomponent reaction. The corresponding dihydropyrimidines were obtained in moderate‐to‐good yields with up to 98 % ee under mild conditions. Based on the experimental results and the observed absolute configurations of the products, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.
Total Synthesis and Initial Structure–Activity Relationships of Longicatenamycin A
Authors: von Nussbaum Franz , Anlauf Sonja , Freiberg Christoph , Benet‐Buchholz Jordi , Schamberger Jens , Henkel Thomas , Schiffer Guido , Häbich Dieter
Published: February 2008

Natural products have provided the majority of lead structures for marketed antibacterials. In addition, they are biological guide principles to new therapies. Nevertheless, numerous “old” classes of antibiotics such as the longicatenamycins have never been explored by chemical postevolution. Longicatenamycin A is the first defined longicatenamycin congener that has been totally synthesized and tested in pure form. This venture required the de novo syntheses of the non‐proteinogenic amino acids (2S,3R)‐β‐hydroxyglutamic acid (HyGlu), 5‐chloro‐D‐tryptophan (D‐ClTrp), and (S)‐2‐amino‐6‐methylheptanoic acid (hhLeu). In the key step, the sensitive HyGlu building block was coupled as a pentafluorophenyl active ester to the unprotected H‐D‐ClTrp‐Glu‐hhLeu‐D‐Val‐D‐(Cbz)Orn‐OH fragment. This first total synthesis of longicatenamycin A provided new congeners of the natural product (deacetyllongicatenamycin, dechlorolongicatenamycin, and longicatenamycin‐A‐amide).
Multi‐institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high‐grade gliomas
Authors: Balmaceda Casilda , Peereboom David , Pannullo Susan , Cheung Ying Kuen K. , Fisher Paul G. , Alavi Jane , Sisti Michael , Chen Johnson , Fine Robert L.
Published: February 2008

BACKGROUND.

The prognosis for patients with recurrent high‐grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice‐daily dosing schedule might be more effective, the safety and efficacy of twice‐daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence.

METHODS.

This multi‐institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m2 of temozolomide was followed by 9 consecutive doses of 90‐mg/m2 every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m2 twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred.

RESULTS.

For GBM, AA, and AO patients, respectively, the median progression‐free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system).

CONCLUSIONS.

Twice‐daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature. Cancer 2008. © 2008 American Cancer Society.
Molecular allelokaryotyping of early‐stage, untreated chronic lymphocytic leukemia
Authors: Lehmann Sören , Ogawa Seishi , Raynaud Sophie D. , Sanada Masashi , Nannya Yasuhito , Ticchioni Michel , Bastard Christian , Kawamata Norihiko , Koeffler H. Phillip
Published: February 2008

BACKGROUND.

To the authors' knowledge, genetic abnormalities in early‐stage chronic lymphocytic leukemia (CLL) have not been examined fully. Single nucleotide polymorphism (SNP) genomic array (SNP‐chip) is a new tool that can detect copy number changes and uniparental disomy (UPD) over the entire genome with very high resolution.

METHODS.

The authors performed SNP‐chip analysis on 56 samples from patients with early‐stage, untreated CLL. To validate the SNP‐chip data, fluorescence in situ hybridization (FISH) analysis was performed at selected sites. Expression levels of ZAP‐70 and the mutational status of immunoglobulin heavy‐chain gene also were examined.

RESULTS.

SNP‐chip analysis easily detected nearly all changes that were identified by FISH, including trisomy 12, deletion of TP53 (17p13), deletion of ATM (11q22), and deletion of 13q14. Only 10 of 56 CLL samples (18%) had no genomic abnormalities. Excluding the 4 common abnormalities mentioned above, 25 CLL samples (45%) had a total of 45 copy number changes detected by SNP‐chip analysis. Four samples had 6q deletion at 6q21 that involved the AIM1 gene. UPD was detected in 4 samples; 2 samples involved whole chromosome 13 resulting in homozygous deletion of micro‐RNA‐15a (miR‐15a)/miR‐16‐1. CLL samples with deletion of 13q14 and trisomy 12 were mutually exclusive.

CONCLUSIONS.

Genetic abnormalities, including whole chromosome 13 UPD, are very common events in early‐stage CLL. SNP‐chip analysis can detect small genetic abnormalities in CLL and may be able to support or even supplant FISH and cytogenetics. Cancer 2008. © 2008 American Cancer Society.