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Angiographic follow-up in 37 patients after radiosurgery for cerebral arteriovenous malformations as part of a multimodality treatment approach.

Modified Linac radiosurgery was utilized at our institution between 1990 and 1995 in 54 patients with cerebral arteriovenous malformations (AVMs) as part of a multimodality therapeutic approach. Most patients also underwent surgery and embolization of the AVMs prior to radiosurgery. The goal of the adjunctive radiosurgical treatment was the complete angiographic obliteration of the deep residual AVM after subtotal embolization and resection. Radiosurgery was used as the primary treatment of some small deep AVMs which were judged to have a high risk of morbidity if approached surgically. Of the 54 patients, 37 have had follow-up angiograms available for review. The median time interval between radiosurgery and the most recent angiogram was 22 months (range 5-66 months). This is a retrospective report on the angiographic follow-up available on this selected group of patients with difficult AVMs. All angiograms were evaluated for the presence of residual AVM. If any residual AVM was present, a decrease in size of more than 50% was noted as significant. The hospital and office charts of all patients were reviewed and the patients and families were contacted for up-to-date clinical follow-up. Prior to treatment, 11 patients had Spetzler-Martin grade 5 AVMs, 12 patients had grade 4 AVMs, and 14 patients had grade 3 AVMs. There were no grade 1 or 2 AVMs treated with radiosurgery. Of these 37 patients, 13 (35%) were completely obliterated on follow-up angiography. Three of the 11 (27%) grade 5 AVMs were completely obliterated. Seven of the 12 (58%) grade 4 AVMs were obliterated. Three of the 14 (21%) grade 3 AVMs have documented radiosurgical obliteration, however 8 others have had a significant decrease in size on the first posttreatment angiogram (median follow-up 14 months) and have further angiographic follow-up pending. There were 5 hemorrhages after radiosurgery, 1 was fatal and 1 resulted in permanent morbidity. Six patients have been reembolized since radiosurgery and 2 of those had their AVMs surgically resected thereafter. Only 1 patient of 6 (17%) in this series who was treated with radiosurgery alone has had documented AVM obliteration. None of 3 treated with embolization alone prior to radiosurgery have had complete obliteration. Three of the 5 patients (60%) who had only surgery prior to radiosurgery had their AVMs completely obliterated. Of the 23 patients who had all three treatments (embolization, surgery, and radiosurgery), 10 (43%) had complete obliteration of their AVMs. One patient (2%) developed moderate permanent neurological disability as a result of radiosurgery-induced necrosis. This patient did have complete obliteration of her AVM. These data support the use of radiosurgery for treatment of cerebral AVMs as part of a multimodality approach if the surgical risk of any residual AVM after embolization and microsurgical resection is deemed excessive. The adjunctive use of radiosurgery in this series resulted in the safe complete obliteration of many very difficult grade 4 and 5 AVMs. These data do not support the use of radiosurgery as the primary treatment of surgically resectable AVMs since there is a risk of interval hemorrhage and the obliteration rate is far inferior to that of microsurgical resection.

Adolescent↗

[Outcome quality of treatment for chronic low back pain under primary care conditions].

BACKGROUND: Little is known about the outcome quality of treatment for chronic low back pain under primary care conditions in Germany. METHODS: All physicians (2100) of middle Franconia, a region of Bavaria with 1.6 million inhabitants, involved in outpatient management were asked to include consecutively patients who suffered from low back pain of at least 4 weeks duration without decreasing intensity. Before and after a 6-month interval patients documented the following outcome data in a questionnaire: pain intensity during the last 24 hours (numerical rating scale), pain-dependent disability (Brief Pain Inventory, German version), health-related quality of life (SF-36, German version), depression (Allgemeine Depressionsskala), pain chronification state (Mainz Pain Staging System) and the days of inability to work within 3 months before start and end of the interval. Treatment of patients was not standardized and included the natural spectrum of non-surgical therapies for low back pain except multimodal pain therapy programs. RESULTS: Thirty-five physicians participated in the study. "Before and after" data of 157 patients (43+/-12 years) could be analysed. Initially 20% were classified in pain chronification state I, 57% in state II and 23% in state III. The pain intensity, pain-dependent disability, depression and quality of life improved significantly but mean differences and effect sizes were small (p<0.41). Less than one third of patients improved by 30% or more from baseline or by one step in the chronification state of pain. Days off work did not change significantly. Predictors for positive therapy response could not be identified. CONCLUSIONS: Monodisciplinary treatment procedures are not sufficient to ameliorate problems of patients in advanced chronification states of back pain.

English Abstract↗

Multimodal classical conditioning of fear: contributions of direct, observational, and verbal experiences to current fears.

The authors propose that a multimodal classical conditioning model be considered when clinicians or clinical researchers study the etiology of fears and anxieties learned by human beings. They argue that fears can be built through the combined effects of direct, observed, and verbally presented classical conditioning trials. Multimodal classical conditioning is offered as an alternative to the three pathways to fear argument prominent in the human fear literature. In contrast to the three pathways position, the authors present theoretical arguments for why "learning by observation" and "learning through the receipt of verbal information" should be considered classical conditioning through observational and verbal modes. The paper includes a demonstration of how data, commonly collected in research on the three pathways to fear, would be studied differently using a multimodal classical conditioning perspective. Finally, the authors discuss implications for assessment, treatment, and prevention of learned fears in humans.

Adolescent↗

Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma.

PURPOSE: We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy. RESULTS: Perioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2-, and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomatous cell disease had 1- and 2-year survival rates of 45% and 7.5%; no patient lived longer than 25 months (P < .01). At resection, positive regional mediastinal lymph nodes were found in 13. Positive lymph nodes were associated with poorer survival than were negative nodes (P < .01). Patients with epithelial variant and negative mediastinal lymph nodes had a survival rate of 45% at 5 years. CONCLUSION: Multimodality therapy including extrapleural pneumonectomy has acceptable morbidity and mortality for selected patients. Prolonged survival occurred in patients with epithelial histologic variant and negative mediastinal lymph nodes. These data provide a rationale for a revised staging system for malignant pleural mesothelioma; furthermore, they permit stratification of patients into groups likely to benefit from aggressive multimodality treatment.

Adult↗

The benefit of neurogenic mixed evoked potentials for intraoperative spinal cord monitoring during correction of severe scoliosis: a case study.

STUDY DESIGN: A case report is presented. OBJECTIVE: To present a case in which surgical correction of a severe scoliotic curve caused unilateral loss of neurogenic mixed evoked potential data despite unchanged somatosensory data. SUMMARY OF BACKGROUND DATA: Surgical correction of large scoliotic curves presents a risk to the function of the spinal cord. Multimodality intraoperative neurophysiologic monitoring of the spinal cord is recommended during such procedures. METHODS: A 13-year-old girl with severe double major scoliosis underwent a staged operative procedure for correction of her spine deformity. Intraoperative neurophysiologic monitoring using somatosensory-evoked potentials and neurogenic mixed evoked potentials was performed for each stage. RESULTS: During the final stage (a T4-L5 posterior instrumentation and fusion) left neurogenic mixed evoked potential data were lost approximately 45 minutes after placement of the left-side, correcting rod. The surgeon was warned of the data change. Set bolts were loosened at all fixation points, and the data quickly returned to within normal limits of baseline. Somatosensory data never approached warning criteria at any point during surgery. The patient awakened with no neurologic deficit. CONCLUSIONS: Neurophysiologic monitoring using both somatosensory-evoked potentials and neurogenic mixed evoked potentials is recommended when surgery is performed to correct spine deformity. The Stagnara wake-up test, somatosensory-evoked potentials, and neurogenic mixed evoked potentials are important components of spinal cord monitoring during surgery, and should be used together for optimal protection of neurologic function.

Adolescent↗

Importance of NMDA receptors for multimodal integration in the deep layers of the cat superior colliculus.

1. Many sensory events contain multimodal information, yet most sensory nuclei are devoted to the analysis of single-modality information. In the deep superior colliculus (DSC), visual, auditory, and somatosensory information converges on individual multimodal neurons. The responses of multimodal neurons are determined by the temporal and spatial correspondence properties of the converging inputs such that stimuli arising from the same event elicit a facilitated multimodal response. 2. N-methyl-D-aspartate (NMDA) receptors may underlie the detection of spatial and temporal coincidence and could be involved in the generation of multimodal facilitatory responses because of the nonlinear properties of NMDA-receptor-mediated events. To assess the role of NMDA receptors in multimodal integration, we made extracellular recordings from single multisensory neurons in the DSC of the cat. 3. The responses to visual, auditory, and somatosensory stimuli alone and to multimodal combinations of stimuli were challenged with iontophoretically applied D-2-amino-5-phosphonovalerate (AP5), an NMDA receptor antagonist. All responses to visual stimuli presented alone (n = 9) were greatly reduced. Somatosensory responses (n = 25) were usually decreased. In contrast, the responses to auditory stimulation were decreased (n = 9), unaffected (n = 3), or enhanced (n = 5). 4. Responses to multimodal stimulus presentations were consistently reduced during iontophoretic application of AP5, irrespective of the modalities that made up the stimulus. The reductions of multimodal responses were significantly greater than the sum of the reductions of responses to single-modality stimuli. 5. The data suggest that for unimodal stimuli, the importance of NMDA receptors in synaptic transmission of sensory responses in DSC may be dependent on the stimulus modality. Furthermore, NMDA receptors are of major importance in the integration of input from different modalities for the generation of multimodal responses.

2-Amino-5-phosphonovalerate↗

First-order statistics of human stabilogram.

We investigated the statistical properties of the centre of pressure (COP) vector during quiet standing, as measured on a force platform. To derive a statistical model for the data, the COP vector, locally averaged COP, and deviations from the average COP were analysed. Whereas indefinite multimodal distributions for the components of the COP were observed, the density functions of deviation from the averaged COP had reproducible properties. The anterior-posterior and mediolateral components of the deviations had in common that they were correlated variables with a non-circular statistic. The main axes of the equiprobability density curves were rotated with respect to the natural anterior-posterior and mediolateral directions. By means of more detailed statistical analysis of the data, two distinct populations of subjects were identified. In some cases we have found Gaussian distributions of the components of deviation from the average COP. In most cases the statistics was non-Gaussian. The average contrast, a new dimensionless characteristic quantity, independent of platform calibration, was introduced as a useful indicator of non-Gaussian effects in the postural control system.

Humans↗

Positron emission tomography in the study of human tumors.

To increase our understanding of cancer and improve cancer treatment on a rational basis we need to identify both qualitative and quantitative differences between normal and neoplastic tissue. The multimodality approach to cancer treatment includes radiotherapy, chemotherapy, hyperthermia, and immunotherapy. Most of the data on which we base our therapeutic strategies have been derived from in vitro studies or animal tumor models. More information is required on the physiology of in vivo human tumors and their response to therapy. Positron emission tomography allows the regional tissue concentration of a positron emitting radionuclide to be measured in absolute units. If valid tracer models can be formulated that accurately describe the fate of an administered "biological" tracer then the physiological process under investigation can be measured quantitatively. The sequential inhalation of C15O2, 15O2, and 11CO allows regional tissue blood flow, oxygen utilization and blood volume to be measured in absolute units. Tissue perfusion, a measure of nutrient (eg, oxygen) supply, drug delivery, or a means of heat dissipation, is of immense importance to oncologists. The oxygen-15 technique has been used not only to study regional blood flow and oxygen utilization in both tumor and normal tissue but also their response to therapeutic intervention. In those studies were tracer models are thought to be less than complete (eg, due to insufficient biological data) then only a semiquantitative or qualitative assessment of the pathophysiological state may be possible. In this respect, tumor function has been characterized by the rate of uptake of 18F-2-deoxyglucose. This technique has provided a means of tumor grading and differentiating between radiation-induced tissue necrosis and tumor recurrence. Metabolic imaging with labeled amino acids appears particularly useful in the delineation of tumor extent. Blood brain barrier integrity and the pharmacokinetics of cytotoxic drugs have also been studied quantitatively. In the future, receptor studies are likely to play an increasing role. In this review dealing with the positron emission tomography oncologic work to date, emphasis has been placed on the physiological information obtainable and how it may further our understanding of cancer and its treatment.

Blood-Brain Barrier↗

Imaging green fluorescent protein fusion proteins in Saccharomyces cerevisiae.

Tagging expressed proteins with the green fluorescent protein (GFP) from Aequorea victoria [1] is a highly specific and sensitive technique for studying the intracellular dynamics of proteins and organelles. We have developed, as a probe, a fusion protein of the carboxyl terminus of dynein and GFP (dynein-GFP), which fluorescently labels the astral microtubules of the budding yeast Saccharomyces cerevisiae. This paper describes the modifications to our multimode microscope imaging system [2,3], the acquisition of three-dimensional (3-D) data sets and the computer processing methods we have developed to obtain time-lapse recordings of fluorescent astral microtubule dynamics and nuclear movements over the complete duration of the 90-120 minute yeast cell cycle. This required low excitation light intensity to prevent GFP photobleaching and phototoxicity, efficient light collection by the microscope optics, a cooled charge-coupled device (CCD) camera with high quantum efficiency, and image reconstruction from serial optical sections through the 6 micron-wide yeast cell to see most or all of the astral molecules. Methods are also described for combining fluorescent images of the microtubules labeled with dynein-GFP with high resolution differential interference contrast (DIC) images of nuclear and cellular morphology [4], and fluorescent images of the chromosomes stained with 4,6-diamidino-2-phenylindole (DAPI) [5].

Dyneins↗

Functional MR imaging: from the BOLD effect to higher motor cognition.

The key contributions of functional imaging to our understanding of the human motor system and higher motor disorders are reviewed in this chapter. Following a short introduction into the method of functional magnetic resonance imaging (fMRI), some core aspects of the human motor system (multiple nonprimary motor areas, the mirror neuron system, intraparietal multimodal cortex) are highlighted. Finally, the convergence (and divergence) of functional imaging and neurological data from patients with lesions of the motor system is discussed with special emphasis to how this informs our current knowledge of the pathophysiology of higher motor disorders.

Brain Mapping↗

Research on day treatment programs for preschoolers with disruptive behavior disorders.

OBJECTIVE: This review examined the literature on psychosocial treatments for preschoolers with disruptive behavior disorders to delineate ways in which interventions developed in research settings can be used to enhance existing clinical preschool day treatment programs. METHODS: A PsycINFO search was performed by using the keywords "day treatment," "behavior problems," "disruptive behavior disorder," and "oppositional defiant disorder" to find articles published between 1974 and 2004 on randomized controlled trials of psychosocial interventions for preschoolers (ages two to five years). No randomized controlled trials of multimodal day treatment programs were found. Therefore, studies on multimodal day treatment were selected on the basis of whether they presented quantitative outcome data. RESULTS AND CONCLUSIONS: Little research was available on the effectiveness of day treatment programs, despite the programs' prevalence as a treatment modality for disruptive preschoolers. In contrast, many interventions in the disruptive behavior disorder research have not made their way into clinical practice. Preschool day treatment programs may be enhanced by improving access to care, emphasizing social problem-solving skills, and using strategies to engage families in treatment. Research studies on existing day treatment programs are needed to clarify the role of these programs in child psychiatry clinics and to shed light on optimal methods of service delivery.

Attention Deficit and Disruptive Behavior Disorder↗

Proposal for a clinical classification of liver metastases.

The lack of a worldwide-accepted classification of liver metastases makes it difficult to compare data on natural history and results from different treatments. The increasing interest in aggressive multimodal therapies for hepatic metastases prompted us to review the chief prognostic factors and the main published classifications in order to propose a new clinical classification, whose principal application concerns metastases from colorectal adenocarcinomas. Following the general rules of the TNM classification, liver metastases are classified by expressing with letters and numbers the parameters selected for their prognostic importance, clinical applicability and objectivity. H (hepatic) is the letter that indicates the liver is the site of metastasis. Synchronous metastases are indicated by H, metachronous by rH (r = recurrent). The extent of liver involvement is defined: H1, liver involvement less than 25%; H2, from 25 to 50%; H3, more than 50%. Site of metastases is defined by s (single), m (multiple to one surgical lobe), b (to both lobes), i (infiltration of important structures). The alteration of liver functions is indicated by F. The presence of cirrhosis is noted by C.

Colonic Neoplasms↗

Emerging advantages and drawbacks of telephone surveying in public health research in Ireland and the U.K.

BACKGROUND: Telephone surveys have been used widely in public health research internationally and are being increasingly used in Ireland and the U.K. METHODS: This study compared three telephone surveys conducted on the island of Ireland from 2000 to 2004, examining study methodology, outcome measures and the per unit cost of each completed survey. We critically examined these population-based surveys which all explored health related attitudes and behaviours. RESULTS: Over the period from 2000 to 2005 the percentage of calls which succeeded in contacting an eligible member of the public fell, from 52.9% to 31.8%. There was a drop in response rates to the surveys (once contact was established) from 58.6% to 17.7%. Costs per completed interview rose from 4.48 euro to 15.65 euro. Respondents were prepared to spend 10-15 minutes being surveyed, but longer surveys yielded poorer completion rates. Respondents were willing to discuss issues of a sensitive nature. Interviews after 9 pm were less successful, with complaints about the lateness of the call. Randomisation from electronic residential telephone directory databases excluded all ex-directory numbers and thus was not as representative of the general population as number generation by the hundred-bank method. However the directory database was more efficient in excluding business and fax numbers. CONCLUSION: Researchers should take cognisance of under-representativeness of land-line telephone surveys, of the increasing difficulties in contacting the public and of mounting personnel costs. We conclude that telephone surveying now requires additional strategies such as a multimode approach, or incentivisation, to be a useful, cost-effective means of acquiring data on public health matters in Ireland and the U.K.

Attitude to Health↗

Treatment of muscle-invasive bladder cancer: progress and new challenges.

The management of muscle-invasive bladder cancer has evolved over the last 20 years. Radical surgery, while curative for a significant number of patients, is inadequate for a subgroup with aggressive features including, but not limited to, advanced local stage, lymphovascular invasion on transurethral resection specimen, or variant histology such as small cell carcinoma. It is now clear that chemotherapy can improve the outcome for such patients. Combination platinum-based neoadjuvant chemotherapy is associated with a survival advantage of 5-8% at 5 years over local therapy alone. Improvements in surgical technique are also important and need to be further refined. Biologic-based staging and targeted therapies hold promise for the future. The critical issue in multimodal therapy for this very heterogeneous disease is individualized patient selection. In this review, data are presented with emphasis on the practical application of current knowledge to the management of patients with muscle-invasive bladder cancer.

Antineoplastic Agents↗

Principles of multimodal imaging.

Current medical practice deals with a variety of multimodal information (X-ray film, ultrasound, CT, MR, ECG and EEG, laboratory results, medical records, etc.) Diagnosis and treatment demand an integrated view of this information including the patient's record and history. This paper describes multimodal imaging approaches to such a system with regard to (i) user interface, (ii) data management (including access control), (iii) registration and modality matching based on reference models, and (iv) interface to the modalities.

Data Display↗

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗

Induction cisplatin and paclitaxel followed by combination chemoradiotherapy with 5-fluorouracil, cisplatin, and paclitaxel before resection in localized esophageal cancer: a phase II report.

BACKGROUND: Multimodality therapy for esophageal cancer holds promise for improving outcome in this lethal disease. On the basis of encouraging data from a phase I trial, we conducted a phase II study of preoperative chemotherapy, followed by concurrent chemoradiotherapy and surgery. METHODS: Patients with clinically staged resectable esophageal cancer were treated with induction cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to eight weeks after multimodality induction, esophagectomy was performed in suitable patients. Study end points were survival, pathologic complete response, and toxicity. RESULTS: Twenty-one patients were enrolled with a median age of 58 years, and all patients were clinically staged II or III. Sixteen (76.2%) patients completed the trial, of whom four (25%) had a pathologic complete response. One patient died from postoperative complications. Grade 3 or 4 toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in 6 of the first 14 patients, thus necessitating a planned dose reduction of paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2-year disease-specific survival for the study population was 78%. CONCLUSIONS: This regimen of multimodality therapy before resection resulted in an encouraging 2-year survival rate but a disappointing rate of pathologic complete response and was toxic, necessitating a predetermined paclitaxel dose reduction. The incorporation of taxanes into induction strategies for esophageal cancer seems promising, but the optimal schedule remains undefined.

Aged↗

Fusing EEG and fMRI based on a bottom-up model: inferring activation and effective connectivity in neural masses.

The elucidation of the complex machinery used by the human brain to segregate and integrate information while performing high cognitive functions is a subject of imminent future consequences. The most significant contributions to date in this field, known as cognitive neuroscience, have been achieved by using innovative neuroimaging techniques, such as electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), which measure variations in both the time and the space of some interpretable physical magnitudes. Extraordinary maps of cerebral activation involving function-restricted brain areas, as well as graphs of the functional connectivity between them, have been obtained from EEG and fMRI data by solving some spatio-temporal inverse problems, which constitutes a top-down approach. However, in many cases, a natural bridge between these maps/graphs and the causal physiological processes is lacking, leading to some misunderstandings in their interpretation. Recent advances in the comprehension of the underlying physiological mechanisms associated with different cerebral scales have provided researchers with an excellent scenario to develop sophisticated biophysical models that permit an integration of these neuroimage modalities, which must share a common aetiology. This paper proposes a bottom-up approach, involving physiological parameters in a specific mesoscopic dynamic equations system. Further observation equations encapsulating the relationship between the mesostates and the EEG/fMRI data are obtained on the basis of the physical foundations of these techniques. A methodology for the estimation of parameters from fused EEG/fMRI data is also presented. In this context, the concepts of activation and effective connectivity are carefully revised. This new approach permits us to examine and discuss some future prospects for the integration of multimodal neuroimages.

Brain↗