bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular Recording from Posterior Cricoarytenoid Motoneurons in the Rat
Authors: Berkowitz Robert G. , Chalmers John , Sun Qi-Jian , Pilowsky Paul
Published: October 2014

The ability to maintain coordinated vocal cord abduction and upper airway patency is dependent on the integrity of the posterior cricoarytenoid (PCA) motoneurons and their multiple neural connections. Study of the PCA motoneurons represents the initial step in understanding the complex mechanisms responsible for coordinated vocal cord abduction and may provide an insight into the possible pathological processes underlying the various clinical presentations of vocal cord dysfunction. Intracellular recordings were made from 11 PCA motoneurons in Sprague-Dawley rats, which all showed an inspiratory augmenting discharge pattern that is also characteristic of phrenic nerve activity. The resting membrane potential was −56 ± 11 mV. Two PCA motoneurons were injected with Neurobiotin to demonstrate neuronal morphology, which was found to be similar to that obtained by retrograde labeling with cholera toxin B subunit. The technique described for intracellular recording of PCA motoneurons should allow more detailed morphological, electrophysiological, and immunohistochemical information to be obtained, to thereby identify some of the factors responsible for maintaining normal function of the PCA muscle.
Motor Innervation of the Human Cricopharyngeus Muscle
Authors: Sasaki Clarence T. , Sims H. Steven , Kim Young-Ho , Czibulka Agnes
Published: October 2014

Innervation of the human cricopharyngeus muscle remains historically controversial and unclear, encouraging numerous treatments inconsistently designed to pharmacologically or mechanically alter the contractile state of this muscle. Neuroanatomic controversy results from and is perpetuated by 1) use of nonhuman models, 2) observational misinterpretation of small-diameter, overlapping nerve fibers, and, most importantly, 3) lack of real-time verification of neural projections. We sought to overcome these difficulties by performing microdissections in 27 patients undergoing laryngectomy and using real-time electromyographic verification. We demonstrated 1) dual ipsilateral innervation by the pharyngeal plexus and recurrent laryngeal nerve, 2) segmental projection of the recurrent laryngeal nerve to anterior motor units, 3) pharyngeal plexus projection to posterior motor units, 4) absence of a sympathetic or external superior laryngeal nerve contribution, and 5) absence of contralateral innervation. Suchdual ipsilateral innervation, segmentally projected, has not been previously described in any other form of neuromuscular organization. Neuroanatomic accuracy should improve diagnostic and therapeutic strategies for future management of pharyngeal dysphagia.
Geometric Structure of the Human and Canine Cricothyroid and Thyroarytenoid Muscles for Biomechanical Applications
Authors: Cox Karin A. , Alipour Fariborz , Titze Ingo R.
Published: October 2014

The geometric structure of the cricothyroid (CT) muscle and thyroarytenoid (TA) muscle was quantified in 6 human and 3 canine larynges. Each muscle was divided into a series of fiber bundles. With a 3-dimensional micrometer probe, the coordinates of the origin and insertion of each bundle were measured before dissection. It was found that the mass of the CT muscle in the dog was 1.463 ± 0.280 g, which was significantly greater than the 0.9423 ±0.123 g found in the human. This was a result of the cross-sectional area of the canine CT muscle being 105.3 ± 11.6 mm2 instead of the 73.8 ± 7.4 mm2 found for the human. However, the ratios of CT/TA mass and cross-sectional area between the two groups were not significantly different, suggesting that the two muscles grow proportionally.
How Do Mobile Phone Diabetes Programs Drive Behavior Change?
Authors: Nundy Shantanu , Mishra Anjuli , Hogan Patrick , Lee Sang Mee , Solomon Marla C. , Peek Monica E.
Published: October 2014

Purpose

The purpose of this study was to investigate the behavioral effects of a theory-driven, mobile phone–based intervention that combines automated text messaging and remote nursing, using an automated, interactive text messaging system.

Methods

This was a mixed methods observational cohort study. Study participants were members of the University of Chicago Health Plan (UCHP) who largely reside in a working-class, urban African American community. Surveys were conducted at baseline, 3 months (mid-intervention), and 6 months (postintervention) to test the hypothesis that the intervention would be associated with improvements in self-efficacy, social support, health beliefs, and self-care. In addition, in-depth individual interviews were conducted with 14 participants and then analyzed using the constant comparative method to identify new behavioral constructs affected by the intervention.

Results

The intervention was associated with improvements in 5 of 6 domains of self-care (medication taking, glucose monitoring, foot care, exercise, and healthy eating) and improvements in 1 or more measures of self-efficacy, social support, and health beliefs (perceived control). Qualitatively, participants reported that knowledge, attitudes, and ownership were also affected by the program. Together these findings were used to construct a new behavioral model.

Conclusions

This study’s findings challenge the prevailing assumption that mobile phones largely affect behavior change through reminders and support the idea that behaviorally driven mobile health interventions can address multiple behavioral pathways associated with sustained behavior change.
False positive or negative results of shear-wave elastography in differentiating benign from malignant breast masses: analysis of clinical and ultrasonographic characteristics
Authors: Kim Mi Young , Choi Nami , Yang Jung-Hyun , Yoo Young Bum , Park Kyoung Sik
Published: October 2014

Background

Shear-wave elastography (SWE) has the potential to improve diagnostic performance of conventional ultrasound (US) in differentiating benign from malignant breast masses.

Purpose

To investigate false positive or negative results of SWE in differentiating benign from malignant breast masses and to analyze clinical and imaging characteristics of the masses with false SWE findings.

Material and Methods

From May to October 2013, 166 breast lesions of 164 consecutive women (mean age, 45.3 ± 10.1 years) who had been scheduled for biopsy were included. Conventional US and SWE were performed in all women before biopsy. Clinical, ultrasonographic morphologic features and SWE parameters (pattern classification and standard deviation [SD]) were recorded and compared with the histopathology results. Patient and lesion factors in the “true” and “false” groups were compared.

Results

Of the 166 masses, 118 (71.1%) were benign and 48 (28.9%) were malignant. False SWE features were more frequently observed in benign masses. False positive rates of benign masses and false negative rates of malignancy were 53% and 8.2%, respectively, using SWE pattern analysis and were 22.4% and 10.3%, respectively, using SD values. A lesion boundary of the masses on US ( P = 0.039) and younger patient age ( P = 0.047) were significantly associated with false SWE findings.

Conclusion

These clinical and ultrasonographic features need to be carefully evaluated in performance and interpretation of SWE examinations.
Country of birth, parental background and self-rated health among adolescents: A population-based study
Authors: Lindström Martin , Modén Birgit , Rosvall Maria
Published: October 2014

Aims: The aim of this study was to investigate differences according to country of birth and parental country of birth, in relation to poor self-rated health (SRH), in Swedish adolescents. Methods: The Scania public health survey among children and adolescents, conducted in 2012, is a cross-sectional study including most pupils in grade 9 (15 years old), including in 32 of 33 municipalities. The participation rate was 83% (9,791 of 11,735). We performed logistic regressions to investigate the association between the students’ country of birth, parental country of birth and poor SRH. Results: Boys born outside Europe had an odds ratio (OR) 2.1 (1.6–2.8) of poor SRH in the unadjusted model, which was reduced to 0.7 (0.4–1.3) in the multiple model, as compared to boys born in Sweden with both or one parent born in Sweden. Boys born in Europe had an OR 0.4 (0.2–0.9) of poor SRH, after multiple adjustments. Girls born in Sweden with both parents born abroad, and girls born outside of Europe had significantly lower ORs of poor SRH in the multiple model. In particular, adjustment for socio-demographic and psychosocial factors reduced the ORs of poor SRH among boys, but did so to a lesser extent among girls. Conclusions: Differences in socio-demographic and psychosocial factors explained the higher odds of poor SRH among boys born outside of Europe. Girls born in Sweden with both parents born abroad, and girls born outside Europe, had significantly lower ORs of poor SRH. Our results indicate that there are gender differences in the factors behind poor self-rated health, according to the country-related background of adolescents in Sweden.
Cohort profile: Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)
Authors: Søgaard Anne Johanne , Meyer Haakon E. , Emaus Nina , Grimnes Guri , Gjesdal Clara Gram , Forsmo Siri , Schei Berit , Tell Grethe S.
Published: October 2014

Aims: This paper describes the history, purpose, data collection and contributions in the research collaboration Norwegian Osteoporosis Epidemiologic Studies (NOREPOS). Methods: NOREPOS encompasses almost 85,000 bone mineral density measurements within Cohort of Norway and data on almost 140,000 hip fractures in Norway 1994–2008. Included are anthropometric measurements, blood pressure, lipids and glucose, and 50 standard questions on sociodemographic factors, diseases and risk factors. Blood samples/DNA are stored. The main research question posed in NOREPOS is why hip fracture rates in Norway are the highest in the world. Data on hip fractures 2009–2013 will be added in 2014. Results: Main findings include: Every hour a Norwegian suffers a hip fracture; hip fracture incidence rates declined after 1999; only 16% of patients used anti-osteoporosis drugs 1 year after hip fracture; 25% of patients died within 1 year after the fracture; 12% suffered a new hip fracture within 10 years; rural dwellers had lower hip and forearm fracture incidence than city dwellers; magnesium in tap water may be protective whereas bacterial contamination, cadmium and lead may be harmful to bone health; low serum vitamin D and E levels were associated with higher hip fracture risk; vitamin A was not associated with fracture risk; and abdominal obesity increased the risk of hip fracture when BMI was accounted for. Conclusions: NOREPOS encompasses a unique source of information for aetiological research, genetic studies as well as for biomarkers of osteoporosis and fractures. Because of the increasing number of elderly people in Europe, hip fractures will continue to pose an international public health and health care challenge.
Aboriginalising the parole process: ‘Culturally appropriate’ adaptations and the Canadian federal parole system
Authors: Turnbull Sarah
Published: October 2014

The increasing ‘diversity’ of penal populations in most western countries over the past three decades raises questions as to the fairness and appropriateness of established penal programmes and practices. In some jurisdictions, penal policy-makers and administrators are being forced to deal with the implications of offender diversities, including race, ethnicity, gender, culture and religion, in policy and planning. In Canada, the pervasive over-representation of Aboriginal individuals in prisons has led to calls for change in how the corrections and parole systems deal with Aboriginal prisoners. This article examines the advent of one ‘culturally appropriate’ adaptation of the parole process, the Elder assisted hearing, introduced in 1992 by the Parole Board of Canada as a means of (1) addressing the problem of over-representation and (2) being responsive to Aboriginal difference. It shows that the ‘Aboriginalisation’ of parole hearing formats is by no means a straightforward process, and is illustrative of the broader challenges that racial, cultural and gender differences pose to contemporary penality.
Impact of feedback on physical activity levels of individuals with chronic obstructive pulmonary disease during pulmonary rehabilitation
Authors: Cruz Joana , Brooks Dina , Marques Alda
Published: October 2014

This study aimed at investigating whether providing feedback on physical activity (PA) levels to patients with chronic obstructive pulmonary disease (COPD) is feasible and enhances daily PA during pulmonary rehabilitation (PR). Patients with COPD participated in a 12-week PR program. Daily PA was measured using activity monitors on weeks 1, 7, and 12, and feedback was given in the following weeks on the number of steps, time spent in sedentary, light, and moderate-to-vigorous intensity activities, and time spent standing, sitting, and lying. Compliance with PA monitoring was collected. Two focus groups were conducted to obtain patients’ perspectives on the use of activity monitors and on the feedback given. Differences in PA data were also assessed. Sixteen patients (65.63 ± 10.57 years; forced expiratory volume in one second (FEV1) 70.31 ± 22.74% predicted) completed the study. From those, only eleven participants used the activity monitors during all monitoring days. Participants identified several problems regarding the use of activity monitors and monitoring duration. Daily steps (  p = 0.026) and standing time (  p = 0.030) were improved from week 1 to week 7; however, the former declined from week 7 to week 12. Findings suggest that using feedback to improve PA during PR is feasible and results in improved daily steps and standing time on week 7. The subsequent decline suggests that additional strategies may be needed to stimulate/maintain PA improvements. Further research with more robust designs is needed to investigate the impact of feedback on patients’ daily PA.
Applications of Dynamic Contrast Enhanced MRI in Oncology: Measurement of Tumor Oxygen Tension
Authors: Wang Z. , Su M-Y. , Nalcioglu O.
Published: October 2014

A new model based on an extension of the Krogh's cylindrical model was developed to calculate tumor oxygen tension ( pO2) from the H-1 dynamic contrast enhanced MRI (DCE-MRI) measurements. The model enables one to calculate the tumor pO2 using the vascular volume fraction (fb) obtained by the DCE-MRI. The proposed model has three parameters. For small values of fb one assumes that there exists a linear relationship between and fb. The constant of proportionality in this case is given by C1 — the oxygen tension per vascular volume fraction. For larger values of fb a modified version of Krogh model using two parameters is developed and here C2 — is the integrated blood oxygen tension, and C3 -given by the combination of the oxygen diffusion coefficient, solubility of oxygen in the tissue, capillary radius, and tissue metabolic consumption rate. The parameters of the model can be determined by performing simultaneous in-vivo F-19 MRI oxygen tension measurement and dynamic Gd-DTPA enhanced MRI on the same tumor. Dynamic MRI data can be used with a compartmental model to calculate tumor vascular volume fraction on a pixel by pixel basis. Then tumor oxygen tension map can be calculated from the vascular volume fraction by the extended Krogh model as described above. In the present work, the model parameters were determined using three rats bearing Walker-256 tumors and performing simultaneous F-19 and DCE MRI on the same tumor. The parameters obtained by fitting the model equation to the experimental data were: C1 = 983.2+ 133.2torr, C2 = 58.20 + 2.4 torr, and C3 = 1.7 + 0.1 torr. The performance of the extended Krogh model was then tested on two additional rats by performing both F-19 and DCE-MRI studies and calculating the pO2 (H-1) using the model and comparing it with the pO2 (F-19) obtained from the F-19 MRI. It was found that the measurements obtained by both techniques had a high degree of correlation [ pO2 (H-1) = (1.01 + 0.07) pO2 (F-19) + (0.91 + 0.05) and r=0.96], indicating the applicability of the proposed model in determining pO2 from the DCE-MRI.
Efficient Tumor Antigen Loading of Dendritic Antigen Presenting Cells by Transimmunization
Authors: Girardi Michael , Berger Carole , Hanlon Douglas , Edelson Richard L.
Published: October 2014

Extracorporeal photochemotherapy (ECP), or photopheresis, was originally introduced for the management of patients with cutaneous T cell lymphoma (CTCL). Today, ECP remains the only FDA approved tumor-targeting selective immunotherapy for the treatment of any cancer. The key cellular events permitting ECP-induced anti-tumor immunity against CTCL are the induction of apoptotis in the malignant T cells, and the induction of monocyte-to-dendritic cell (DC) differentiation. In standard ECP, leukocytes extracorporeally exposed to psoralen and ultraviolet A light (UVA) are circulated back to the patient. However, recent findings suggest that co-incubation of these cells prior to re-infusion allows for more efficient phagocytosis and processing of the apoptotic malignant T cells by the newly formed DCs. Moreover, such a co-incubation step permits the direct external manipulation of this system and the design of strategies to augment the production of tumor-loaded DCs. These considerations have led to the development of Transimmunization, so named because it causes transfer of tumor antigens to newly formed dendritic cells capable of initiating immunization against the tumor cells, as the replacement technology for ECP. We will review the scientific understanding of ECP and explain how this can lead a more efficienct, potentially broadly applicable, immunotherapy for cancer.
Enhancing the Effectiveness of Drug-based Cancer Therapy by Electroporation (Electropermeabilization)
Authors: Rabussay Dietmar P. , Nanda Gurvinder S. , Goldfarb Paul M.
Published: October 2014

Many conventional chemotherapeutic drugs, as well as DNA for cancer gene therapy, require efficient access to the cells' interior to be effective. The cell membrane is a formidable barrier to many of these drugs, including therapeutic DNA constructs. Electropermeabilization (EP, often used synonymously with “electroporation”) has become a useful method to temporarily increase the permeability of the cell membrane, allowing a broad variety of molecules efficient access to the cell interior. EP is achieved by the application of short electrical pulses of relatively high local field strength to the target tissue of choice. In cancer therapy, EP can be applied in vivo directly to the tumor to be treated, in order to enhance intracellular uptake of drugs or DNA. Alternatively, EP can be used to deliver DNA into cells of healthy tissue to achieve longer-lasting expression of cancer-suppressing genes. In addition, EP has been used in ex vivo therapeutic approaches for the transfection of a variety of cells in suspension. In this paper, we communicate results related to the development of a treatment for squamous cell carcinomas of the head and neck, using electropermeabilization to deliver the drug bleomycin in vivo directly into the tumor cells. This drug, which is not particularly effective as a conventional therapeutic, becomes highly potent when the intracellular concentration is enhanced by EP treatment. In animal model experiments we found a drug dose of 1 U/cm3 tumor tissue (delivered in 0.25 mL of an aqueous solution/cm3 tumor tissue) and an electrical field strength of 750 V/cm or higher to be optimal for the treatment of human squamous cell tumors grown subcutaneously in mice. Within 24–48 hours, the majority of tumor cells are rapidly destroyed by this bleomycin-electroporation therapy (B-EPT). This raises the concern that healthy tissue may be similarly affected. In studies with large animals we showed that normal muscle and skin tissue, normal tissue surrounding major blood vessels and nerves, as well as healthy blood vessels and nerves themselves, are much less affected than tumor tissue. Normal tissues did show acute, focal, and transitory effects after treatment, but these effects are relatively minor under standard treatment conditions. The severity of these effects increases with the number of electric pulse cycles and applied voltage. The observed histological changes resolved 20 to 40 days after treatment or sooner, even after excessive EP treatment. Thus, B-EPT is distinct from other ablative therapies, such as thermal, cryo, or photodynamic ablation, which equally affect healthy and tumor tissue. In comparison to surgical or radiation therapy, B-EPT also has potential as a tissue-sparing and function-preserving therapy. In clinical studies with over 50 late stage head and neck cancer patients, objective tumor response rates of 55–58%, and complete tumor response rates of 19–30% have been achieved.
The Potential Role of Fourier Transform Infrared Spectroscopy and Imaging in Cancer Diagnosis Incorporating Complex Mathematical Methods
Authors: Schultz Christian P.
Published: October 2014

Infrared spectroscopy and imaging technology can provide new diagnostic capabilities for cancer research applications and to physicians directly involved in patient treatment. A methodology that permits the phenotypical description of cells and tissues is introduced, as well as a variety of new evaluation techniques that allow researchers and physicians to evaluate the infrared data at different levels of sophistication. The detection of cell alterations in the case of Chronic Lymphocytic Leukemia (CLL) demonstrates the capability of infrared spectroscopy to identify and stage this type of cancer, providing new prospects for diagnosis and treatment. The pathological study of oral tissue affected by Squamous Cell Carcinoma (SCC) illustrates the potential of Infrared Spectroscopy and Imaging for tissue diagnosis and cancer staging based in altered cell biochemistry, without using stains or any other marker technology. An example of combined fluid, cell and tissue analysis of thyroid cancers based on infrared technology is introduced to demonstrate the possibility of earlier detection of gland abnormalities and biochemical alterations in cell extracts using fine needle aspirates. Simple statistical techniques such as bivariate histogram analysis can distinguish between normal and altered cells and tissues when applied to infrared spectra and images. More complex mathematical techniques such as Principal Component Analysis (PCA) or Artificial Neural Networks (ANN) provide additional evaluation capabilities that can relate spectra of an unknown sample to an infrared reference database of known cell states. It is documented how this new infrared technology could enhance the diagnoses, treatment decisions and prognoses of patients in the field of cancer medicine.
Brain Metastases from Gynecological Cancers: Factors that Affect Overall Survival
Authors: Mahmoud-Ahmed Ashraf S. , Kupelian Patrick A. , Reddy Chandana A. , Suh John H.
Published: October 2014

We retrospectively reviewed factors that affected overall survival for patients with gynecological cancers that had metastasized to the brain. Between January 1985 to November 1999, we treated 25 patients with brain metastases from gynecological malignancies (cervix n=6, endometrium n=10, and ovary n=9). Various patient and tumor characteristics were identified and analyzed for their significance. Median age was 46 years old (range, 37–78 years) with the majority of tumors being adenocarcinoma (20/25 patients). The treatment consisted of whole brain radiation therapy (WBRT) in 11 patients, focal therapy (surgery and/or stereotactic radiosurgery [SRS]) in 6 patients, and combination therapy (WBRT and surgery and/or SRS) in 8 patients and resulted in median survivals of 6 months, 7 months and 11 months, respectively. Overall median survival was 7.3 months (range, 1 to 88 months). Cause of death was systemic in 9, neurologic in 8 and progression of primary in 2. Those with single lesions had better median survivals compared to those with multiple lesions (17 months vs. 3 months, p=0.017). Our results suggest that patients with a single lesion had improved outcomes. We encourage enrollment of patients with brain metastases onto prospective clinical trials.
Highly Efficient, Large Volume Flow Electroporation
Authors: Li Lin-Hong , Shivakumar Rama , Feller Stephanie , Allen Cornell , Weiss Jonathan M. , Dzekunov Sergey , Singh Vin , Holaday John , Fratantoni Joseph , Liu Linda N.
Published: October 2014

Electroporation is widely used to transfect and load cells with various molecules. Traditional electroporation using a static mode is typically restricted to volumes less than 1 mL, which limits its use in clinical and industrial bioprocessing applications. Here we report efficient, large volume transfection results by using a scalable-volume electroporation system. Suspended (Jurkat) and adherent cells (10T1/2 and Huh-7) were tested. A large macromolecule, FITC-conjugated dextran (MW=500 kD) was used to measure cell uptake, while a plasmid carrying the gene coding for enhanced green fluorescence protein (eGFP) was used to quantitate the flow electrotransfection efficiency as determined by flow cytometry. The flow electroloading efficiency of FITC-dextran was >90%, while the cell viability was highly maintained (>90%). High flow electrotransfection efficiency (up to 75%) and cell viability (up to 90%) were obtained with processing volumes ranging from 1.5 to 50 mL. No significant difference of electrotransfection efficiency was observed between flow and static electrotransfection. When 50 mL of cell volume was processed and samples collected at different time points during electroporation, the transgene expression and cell viability results were identical. We also demonstrated that DNA plasmid containing EBNA1-OriP elements from Epstein-Barr virus were more efficient in transgene expression than standard plasmid without the elements (at least 500 too 1000-fold increase in expression level). Finally, to examine the feasibility of utilizing flow electrotransfected cells as a gene delivery vehicle, 10T1/2 cells were transfected with a DNA plasmid containing the gene coding for mIL12. mIL12 transfected cells were injected subcutaneously into mice, and produced functional mIL12, as demonstrated by anti-angiogenic activity. This is the first demonstration of efficient, large volume, flow electroporation and the in vivo efficacy of flow electrotransfected cells. This technology may be useful for clinical gene therapy and large-scale bioprocesses.
Dual-Modality Imaging of Cancer with SPECT/CT
Authors: Hasegawa Bruce H. , Wong Kenneth H. , Iwata Koji , Barber William C. , Hwang Andrew B. , Sakdinawat Anne E. , Ramaswamy Mohan , Price David C. , Hawkins Randall A.
Published: October 2014

Dual-modality imaging is an in vivo diagnostic technique that obtains structural and functional information directly from patient studies in a way that cannot be achieved with separate imaging systems alone. Dual-modality imaging systems are configured by combining computed tomography (CT) with radionuclide imaging (using positron emission tomography (PET) or single-photon emission computed tomography (SPECT)) on a single gantry which allows both functional and structural imaging to be performed during a single imaging session without having the patient leave the imaging system. A SPECT/CT system developed at UCSF is being used in a study to determine if dual-modality imaging offers advantages for assessment of patients with prostate cancer using111 In-ProstaScint®, a radiolabeled antibody for the prostate-specific membrane antigen.111 In-ProstaScint® images are reconstructed using an iterative maximum-likelihood expectation-maximization (ML-EM) algorithm with correction for photon attenuation using a patient-specific map of attenuation coefficients derived from CT. The ML-EM algorithm accounts for the dual-photon nature of the111 In-labeled radionuclide, and incorporates correction for the geometric response of the radionuclide collimator. The radionuclide image then can be coregistered and overlaid in color on a grayscale CT image for improved localization of the functional information from SPECT. Radionuclide images obtained with SPECT/CT and reconstructed using ML-EM with correction for photon attenuation and collimator response improve image quality in comparison to conventional radionuclide images obtained with filtered backprojection reconstruction. These results illustrate the potential advantages of dual-modality imaging for improving the quality and the localization of radionuclide uptake for staging disease, planning treatment, and monitoring therapeutic response in patients with cancer.
Congruent MRI and Near-infrared Spectroscopy for Functional and Structural Imaging of Tumors
Authors: Gulsen Gultekin , Yu Gultekin , Wang Jun , Nalcioglu Orhan , Merritt Sean , Bevilacqua Frederic , Durkin Anthony J. , Cuccia David J. , Lanning Ryan , Tromberg Bruce J.
Published: October 2014

We present a combined near-infrared diffuse optical spectroscopy (DOS) and Magnetic Resonance Imaging (MRI) system for the study of animal model tumors. Acombined broadband steady-state and frequency domain optical spectroscopy apparatus was integrated with the MRI. The physiological properties of tissue rendered by MRI, including vascular volume fraction and water, were compared with chromophore concentrations as determined from the parameters obtained by optical measurements. DOS measurements provided oxyhemoglobin, deoxy-hemoglobin, and water concentration locally in tumors. A method for coregistration of the information obtained by both modalities was developed. Using Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, illustrating which tissue structure was probed optically. Finally, two optical contrast agents, indocyanine green (ICG) and methylene blue (MB), were employed and their kinetics were measured by DOS system from different locations on the tumor and compared with Gd-DTPA enhancement maps obtained from MRI.
Comparison of Volume-rendered and Surface-rendered MR Colonography
Authors: Heuschmid Martin , Schaefer Juergen F. , Stuecker Dietmar , Vonthein Reinhard , Luboldt Wolfgang , Claussen Claus D. , Seemann Marcus D.
Published: October 2014

In the United States and Europe, colorectal cancer is the second leading cause of cancer-related deaths. It is well known that colorectal carcinomas may originate from preexisting adenomas. For the visualization of colorectal cancer and other pathologic changes such as polyps, two 3D methods (volume-rendering (VR) and surface-rendering (SR)) in MR colonography were compared in our study. MR colonography was carried out in 17 patients on a 1.5 T MR scanner using a 10 mmolar gadolinium water solution enema. Coronal as well as rotated VR and SR views were compared in order to examine the technical quality (TQ) of the visualization model and grade of confidence (GC) in the pathological findings. Colonoscopic findings revealed 8 colorectal carcinoma, 10 patients with polyps, 4 diverticular disease, and 2 with redundant bowel loops. Based on a total of 248 colonic segments for both visualization methods, volume rendering were significantly superior to surface rendering for both, TQ (p<0.0001) and GC (p<0.0001). Volume rendering and surface rendering were not dependent on individual colon segments (p=0.13 for TQ and p=0.18 for GC) or on image rotation (p=0.06 for TQ and p=0.062 for GC). It is also independent of the type of pathology (p=0.31 for TQ and p=0.42 for GC) and the reviewers (p=0.62 for TQ and p=0.88 for GC). This indicates, that for the purpose of interpreting the technical quality and pathological findings, volume rendering is superior to surface rendering in MR colonography. Volume rendering could be used as an 3D visualization tool, enabling MR colonography examinations to be completed sooner in cases where colon distension is sufficient, and it would also provide an overview of potential mass lesions.
Intraoperative MR-Guided Instillation of Phosphorum-32 for Cystic Craniopharyngiomas: Case Report
Authors: Hall Walter A. , Liu Haiying , Truwit Charles L.
Published: October 2014

Intraoperative magnetic resonance imaging has been applied to a number of neurosurgical disease processes since the late 1990's. The ability to visualize the operative site in near-real time has added a significant degree of safety to the treatment of lesions such as a cystic craniopharyngioma which can be located in regions of the brain where an untoward consequence can result in significant neurological morbidity. Previous surgical techniques, although often successful, did not allow the neurosurgeon to directly visualize whether the goals of surgery had been met or whether there was an inadvertent complication associated with the surgical approach until after the event had occurred. The safe and accurate instillation of radioactive phosphorus into this cystic tumor resulted in clinical improvement and the maintenance of normal pituitary function for this patient. The extreme accuracy and safety of this surgical technique is demonstrated by the imaging examples provided.
Evaluation of TNF-α/Bax Gene Therapy and Radiation against C6 Glioma Xenografts
Authors: Gridley Daila S. , Timiryasova Tatyana M. , Miller Glen M. , Andres Melba L. , Dutta-Roy Radha , Bayeta Erben J. M. , Fodor Istvan
Published: October 2014

Successful therapy of high-grade tumors of the brain is likely to require a combination of new therapeutic approaches. The major goal of the present study was to construct a plasmid-based bax gene vector (pGL1-Bax) and evaluate its expression in vitro and in vivo using athymic mice with subcutaneously growing C6 glioma. Preliminary experiments of efficacy and safety were also performed using pGL1-Bax alone and in combination with previously constructed pGL1-TNF-α, as well as with radiation. pGL1-Bax was expressed by C6 cells and was correlated with apoptosis, indicating that the construct and the bax protein were functional. Although intratumoral injections of pGL1-Bax alone, up to total doses of 450 μg, did not significantly affect tumor growth, consistently smaller tumors were obtained when pGL1-TNF-α plus pGL1-Bax were injected 16–18 hr prior to tumor irradiation. Furthermore, in mice with two tumors, one treated and one untreated, progression of the untreated tumor was delayed in the animals receiving all three modalities. No prohibitive toxicities were noted, based on mouse body weights and in vitro assays of blood and spleen. Significant increases in spleen mass, total leukocyte counts, percentage of granulocytes, spontaneous blastogenesis, and CD71-expressing B cells were primarily associated with tumor presence and not treatment type. Overall, the results are promising and suggest that TNF-α/Bax gene therapy may be beneficial against highly malignant tumors of the brain. To our knowledge, this is the first report of bax gene therapy used together with radiation in an in vivo glioma model.
A Review of Stereotactic Radiosurgery in the Management of Brain Metastases
Authors: Sperduto Paul W.
Published: October 2014

This review addresses the epidemiology, historical reports, current issues, data and controversies involved in the management of brain metastases. The literature regarding surgery, whole brain radiation therapy, stereotactic radiosurgery or some combination of those treatments is discussed as well as issues of cost-effectiveness. Ongoing prospective randomized trials will further elucidate the optimal management for patients with brain metastases. Until those data are available, clinicians are encouraged to apply the existing data reviewed here in conjunction with best clinical judgment. A brief clinical guide is as follows. Patients with a solitary metastasis in an operable location and symptomatic mass effect should undergo surgery. Patients with poor performance status (KPS < 70) or more than three brain metastases should receive WBRT alone. Patients with 1-3 brain metastases and KPS ≥ 70, should receive WBRT + SRS. If the patient refuses WBRT or needs salvage after WBRT, then SRS alone is appropriate. Clinicians should not be too dogmatic and should always apply the best clinical judgment.
Stereotactic Radiosurgery in the Management of Intracranial Gliomas
Authors: Roberge David , Souhami Luis
Published: October 2014

Glial neoplasms are the most common primary intracranial malignancies. Treatment of high-grade gliomas has been frustrating, with less than 5% of patients surviving 5 years after a diagnosis of glioblastoma multiforme (GBM). Stereotactic radiosurgery (SRS) and fractionated strereotactic radiotherapy (F-SRT) provide means to either escalate the dose in primary treatment or to palliate recurrences. Because of their lower α/β ratios and more focal nature, low-grade gliomas (LGG) are more attractive targets for stereotactically focused radiation.

Results of available phase I-II data are reviewed for both low and high-grade gliomas. In the case of high-grade gliomas disappointing preliminary phase III data from RTOG 93-05 are discussed.

Toxicity of SRS is discussed. Acute treatment toxicity of significance is unusual and generally self-limited. Occasionally an exacerbation of existing symptoms occurs. Late complications attributable to SRS are usually defined as necrosis within the treatment volume. The rate of necrosis can be hard to define in high-grade gliomas as tumor cells are often present in surgical specimens.

New strategies in the application of stereotactic radiation are touched upon, these include: changes in planning and fractionation, concurrent use of chemotherapy, use of radiation modifiers and biologic agents.

After reviewing the current data for high-grade gliomas, it appears that any apparent improvement in outcome seen in phase I-II trials is attributable to patient selection. The best evidence available does not support the use of SRS for primary high-grade gliomas. The somewhat limited experience in LGG also indicates a lack of benefit for patients treated with stereotactic radiosurgery or F-SRT. For a very select group of patients with small recurrent lesions, F-SRT may represent a safe, reasonable treatment.
Stereotactic Radiosurgery for Benign Neoplasms
Authors: DiBiase Steven J. , Chin Lawrence S.
Published: October 2014

Over the last decade, the use of stereotactic radiosurgery (SRS) for the treatment of intracranial lesions has grown significantly. In addition to malignant brain tumors and vascular malformations, benign tumors have also been treated with SRS. Although surgical resection has long been considered the gold standard in the management of such benign lesions, the outcomes of SRS in various benign neoplasms appears to be comparable. In this review, we will examine the literature as it pertains to the treatment of benign brain tumors with SRS. Of particular note, we will examine the results of SRS in acoustic neuromas, meningiomas, pituitary adenomas, and other benign tumors.
Immunotherapy of Cancer by Active Vaccination: Does Allogeneic Bone Marrow Transplantation after Non-Myeloablative Conditioning Provide a New Option?
Authors: Zöller Margot
Published: October 2014

The critical role of antigen-specific T cells in cancer immunotherapy has been amply demonstrated in many model systems. Though success of clinical trials still remains far behind expectation, the continuous improvement in our understanding of the biology of the immune response will provide the basis of optimized cancer vaccines and allow for new modalities of cancer treatment. This review focuses on the current status of active therapeutic vaccination and future prospects. The latter will mainly be concerned with allogeneic bone marrow cell transplantation after non-myeloablative conditioning, because it is my belief that this approach could provide a major breakthrough in cancer immunotherapy.

Concerning active vaccination protocols the following aspects will be addressed: i) the targets of immunotherapeutic approaches; ii) the response elements needed for raising a therapeutically successful immune reaction; iii) ways to achieve an optimal confrontation of the immune system with the tumor and iv) supportive regimen of immunomodulation. Hazards which one is most frequently confronted with in trials to attack tumors with the inherent weapon of immune defense will only be briefly mentioned.

Many question remain to be answered in the field of allogeneic bone marrow transplantation after non-myeloablative conditioning to optimize the therapeutic setting for this likely very powerful tool of cancer therapy. Current considerations to improve engraftment and to reduce graft versus host disease while strengthening graft versus tumor reactivity will be briefly reviewed. Finally, I will discuss whether tumor-reactive T cells can be “naturally” maintained during the process of T cell maturation in the allogeneic host. Provided this hypothesis can be substantiated, a T cell vaccine will meet a pool of virgin T cells in the allogeneically reconstituted host, which are tolerant towards the host, but not anergised towards tumor antigens presented by MHC molecules of the host.
Photodynamic Therapy for the Treatment of Skin Disease
Authors: Kendall C. A. , Morton C. A.
Published: October 2014

The efficacy of photodynamic therapy for the treatment of a large number of skin diseases, in particular non-malignant skin cancer, has been reported by a number of studies. It has been demonstrated to be particularly beneficial for large or multiple lesions, especially where good cosmesis is required. However for PDT to become established in routine clinical practice further comparative multi-center studies with currently accepted standard techniques are required.
New Light on the Brain: The Role of Photosensitizing Agents and Laser Light in the Management of Invasive Intracranial Tumors
Authors: Eljamel M. Sam
Published: October 2014

Invasive intracranial tumors, particularly malignant gliomas, are very difficult to eradicate surgically and carry a dismal prognosis. The vast majority relapse locally indicating that their cure is dependent on radical and complete local excision. However, their ability to invade and hide among normal brain tissue, our inability to visualize and detect them, the low tolerance of brain tissue to ionizing radiation and the presence of the blood brain barrier are the main causes of our failure to eradicate them. Photodynamic detection with 100% specificity and more than 80% sensitivity offers an excellent chance of visualizing camouflaged tumor nests. Also, photodynamic therapy offers a very good chance of targeted destruction of the remaining tumor cells safely following surgical excision and may double the survival of patients harboring these awful tumors. More work needs to be done to refine this promising technology to exploit it to its full potential.
Clinical Outcomes of Photodynamic Therapy for Head-and-Neck Cancer
Authors: Lou Pei-Jen , Jones Linda , Hopper Colin
Published: October 2014

Head-and-neck cancers not only carry poor prognoses, but also reduced quality of life for the patients. Disease control is often achieved at the expense of substantial functional loss and disfigurement. Photodynamic therapy (PDT) is particularly well suited to the treatment of head-and-neck-tumors because it has little effect on underlying functional structures and has an excellent cosmetic outcome. Studies in the past decades have shown that PDT is of similar efficacy as traditional measures in the treatment of early-stage head-and-neck cancers with an overall response rate of 85%–100%, with up to 75% of the complete responses sustained at 2 years after PDT. For advanced head-and-neck cancers, studies were also conducted to evaluate the palliative effects of PDT. Overall, a 58%–70% palliative benefit can be observed in these patients. Using interstitial PDT, the median survival of the patients with recurrent unresectable head-and-neck cancers can be improved to 14 months (cf. 226 days by using surface illumination PDT). PDT is thus a therapeutic option that may prove a useful addition to the armamentarium of the integrated head and neck oncology team.
Salvage Reimplantation in Patient with Local Recurrent Prostate Carcinoma after Brachytherapy with Three Dimensional Computed Tomography-Guided Permanent Pararectal Implant
Authors: Koutrouvelis Panos , Hendricks Fred , Lailas Niko , Gil-Montero Guillermo , Sehn James , Khawand Nabil , Bondy Harold , Katz Stuart
Published: October 2014

Thirty-one [31] patients with local recurrent or residual adenocarcinoma of the prostate, with no evidence of distant metastases, were treated with second permanent implant using a stereotactic three dimensional system and posterior pararectal CT-guided method. All patients had extensive under local anesthesia or IV sedation pararectal CT-guided biopsy of the prostate and seminal vesicles. All patients except one had 3 month neoadjuvant androgen ablation prior to salvage reimplantation. Twenty [20] of these patients had local recurrence in the prostate and eleven [11] patients had seminal vesicle invasion which was not diagnosed nor treated with the initial brachytherapy. In addition, the patients had PSA failure or local palpable disease, “cold spots” with CT imaging or areas of dosage less than 80% of the prescribed dose with DVH (dose volume histogram). Initial prescribed dose was 120 Gy with103 Pd loose seeds in 26 patients and 144 Gy with125 I loose seeds in 5 patients. For the reimplant the dosage in the recurrent site was 100–144 Gy with125 I seeds in strand in 24 patients (77%) and 100–120 Gy with103 Pd loose seeds in 7 patients (23%). The preference of125 I seeds in the second treatment was because only125 I in strand was available at the time of the reimplant. Eleven [11] patients had second implant twelve to twenty-four months after the initial implant and 20 patients had after twenty-five to eighty-seven months and median follow-up was thirty months. A high level of biochemical control (87%) was achieved in all of these patients who are recognized as high risk due to local recurrence. Four [4] patients experienced grade 2 or 3 GI or GU complications and two [2] patients experienced grade 4 GI complications. Patients with local recurrent prostate cancer following initial brachytherapy including those with seminal vesicle invasion can be successfully treated with pararectal stereotactic CT-guided reimplantation. Assessment of seminal vesicle status is an essential part of staging for local recurrence.