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At least 1,621 records · Page 90Linked to original sources
PubMed2002

The interferon-alpha/beta system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors.

The efficient induction of interferons alpha and beta (IFN-alpha/beta) in virus-infected cells is central to the antiviral response of a host and is regulated mainly at the level of gene transcription. Once produced, IFN-alpha/beta transmit signals to the cell interior via a specific receptor complex to induce an antiviral response. Recently, the auto-amplification mechanism of the IFN-alpha/beta system that follows viral infection has been identified. This mechanism is mediated by transcription factors of the IFN regulatory factor family and, in fact, may have evolved to render the system more robust in antiviral responses.

Animals↗
PubMed2000

Medical management of unresectable, recurrent low-grade retroperitoneal liposarcoma: integration of cytotoxic and non-cytotoxic therapies into multimodality care.

Liposarcomas of the retroperitoneum are rare tumors, and best managed by an expert multidisciplinary team consisting of a surgical oncologist with appropriate medical oncology and radiation oncology collaboration. For large tumors, surgical excision with wide margins is difficult to achieve, and even wide margins cannot ensure that microscopic remnants of residual disease will not grow back in the future. For these reasons, even following expert resection, local recurrence is common. For patients with recurrent and unresectable liposarcoma, treating the sarcoma while maintaining quality of life becomes the major therapeutic goal. Importantly, patients with advanced recurrent disease demonstrate the need for multidisciplinary team involvement, with timely consideration of palliative surgical, radiation therapy, and chemotherapy options. Such patients also represent ideal candidates for investigational approaches aimed at identifying new agents with which to treat this disease. In addition to the development of new cytotoxic agents, patients may be candidates for novel strategies such as differentiation therapies or anti-angiogenic approaches. The recent explosion of knowledge regarding the cytogenetics, molecular, and cellular biology of liposarcomas allows us to remain positive that new translational therapies will be developed to improve the clinical outcomes of patients with these diseases. Current strategies, such as the use of PPARgamma ligands to differentiate liposarcomas, will soon be tested in major national collaborative trials, and the cooperation of surgeons and medical oncologists at all levels of community and academic practice will be crucial to obtain answers in this field. This review will summarize an illustrative case in the process of describing the natural history and potential interventions which should be considered for patients with this disease.

Chromans↗
PubMed1993

Multimodality evoked potentials (auditory, somatosensory and motor) in coma.

Auditory brainstem responses (ABRs) have proved to be significantly related to outcome, both in severe head injury and brain hemorrhage. Nevertheless, the usefulness of ABR is limited by the anatomic extent of the investigated pathways. The combined use of ABRs and somatosensory evoked potentials (SEPs) improves the outcome prediction in comparison to the use of only one modality. It mainly decreases the rate of false negatives, since patients with severe hemispheric damage sparing the brain stem may have a poor outcome despite normal ABRs. The use of motor evoked potentials (MEPs) from magnetic transcranial stimulation is also significantly related to outcome: it appears to be far superior to the clinical evaluation of motor responses, while the combined use of MEPs and SEPs gives a new opportunity of checking sensorimotor dysfunction. ABRs and SEPs may also be useful tools in the confirmation of brain death, the kernel of which is the assessment of brainstem death: they allow to check lemniscal pathways, which cannot be properly evaluated by clinical examination, and provide an objective confirmation of absence of brain stem activity.

Acoustic Stimulation↗
PubMed1997

Diagnostic value of multimodal evoked potentials in HIV-1 infected children.

Evoked potentials (EP) help guide the diagnosis of central nervous system involvement in demyelinating pathologies regarding both children and adults, and in human immunodeficiency virus-1 (HIV-1) correlated pathologies only in regard to adult patients. EP have been shown to be useful in highlighting early signs of the disease. We therefore studied EP in HIV-1 infected children with the aim of verifying the association of results with disease progression, clinical signs and electroencephalogram, and individualizing the most reliable test. Thirty-six patients (20 male and 16 female subjects, age range: 10 months to 12 years) belonging to a group of 45 symptomatic subjects seen at the Pediatric Department were included into the study from November 1991 to December 1994. Ten presented with neurological signs as of disease onset, eight others developed encephalopathy during the follow-up. One hundred seventeen EP, i.e., 27 pattern visual, 64 flash visual and 26 brain stem auditory EP, were recorded. Univariate statistical analysis using the Wilcoxon-Mann-Whitney U test and Student's t test was done. As a whole, we found 22.5% of abnormal EP in subjects without neurological signs and 28.3% in subjects with neurological signs. Results that were obtained suggested a close relationship between both the pattern of visual and brain stem auditory EP exams and disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Multimodal integration of high-resolution EEG and functional magnetic resonance imaging data: a simulation study.

Previous simulation studies have stressed the importance of the use of fMRI priors in the estimation of cortical current density. However, no systematic variations of signal-to-noise ratio (SNR) and number of electrodes were explicitly taken into account in the estimation process. In this simulation study we considered the utility of including information as estimated from fMRI. This was done by using as the dependent variable both the correlation coefficient and the relative error between the imposed and the estimated waveforms at the level of cortical region of interests (ROI). A realistic head and cortical surface model was used. Factors used in the simulations were the different values of SNR of the scalp-generated data, the different inverse operators used to estimated the cortical source activity, the strengths of the fMRI priors in the fMRI-based inverse operators, and the number of scalp electrodes used in the analysis. Analysis of variance results suggested that all the considered factors significantly afflict the correlation and the relative error between the estimated and the simulated cortical activity. For the ROIs analyzed with simulated fMRI hot spots, it was observed that the best estimation of cortical source currents was performed with the inverse operators that used fMRI information. When the ROIs analyzed do not present fMRI hot spots, both standard (i.e., minimum norm) and fMRI-based inverse operators returned statistically equivalent correlation and relative error values.

Analysis of Variance↗
PubMed2003

Intraoperative radiation therapy in the multimodality approach to hepatobiliary tract cancer.

IOERT is a reasonable option to consider in patients who have biliary tract cancers above AJCC or Bismuth stage I disease. Inherent resistance of biliary tract cancer cells to ionizing radiation would indicate that IOERT alone would not eradicate most of the tumor clonagen. EBRT (either preoperatively or postoperatively) should be used in combination with IOERT at experienced institutions that have access to both modalities. The single IOERT dose ranges are 10 to 20 Gy [55,67], whereas the EBRT dose ranges from 45 to 50 Gy in 25 to 28 fractions [67]. The most common energy level used is 8 MeV or less. In addition, IOERT port sizes of less than 6 cm in diameter, and often 4 cm or less, are recommended. Finally, intraoperative reconstruction of severely damaged blood vessels may decrease the clinical manifestation of radiation-induced injury to vessels [68].

Adenocarcinoma↗
PubMed2003

Intraoperative radiotherapy in the multimodality approach to bone and soft tissue cancers.

IORT is a powerful tool for the management of cancer and has been shown to improve local control in the treatment of sarcomas in one prospective, randomized, controlled trial. IORT allows dose escalation in areas where escalation with EBRT would cause potentially excessive acute or late normal tissue toxicity. It has a unique toxicity profile but remains safe and effective when used in appropriately selected patients. In addition, IORT is becoming more widely available at different cancer centers and offers great flexibility in treatment planning for a wide variety of malignancies. As IORT use becomes more common, special care will be required to ensure that it is used by a multidisciplinary team of radiation oncologists and surgeons to ensure the best results for patients.

Adult↗
PubMed2002

Multimodality diagnosis of liver tumors: feature analysis with CT, liver-specific and contrast-enhanced MR, and a computer model.

RATIONALE AND OBJECTIVES: The purpose of this study was to measure and to clarify the diagnostic contributions of image-based features in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. MATERIALS AND METHODS: Six experienced abdominal radiologists each read images from 146 cases (including a contrast material-enhanced computed tomographic [CT] scan and contrast-enhanced and unenhanced magnetic resonance [MR] images) following a checklist-questionnaire requiring them to rate quantitatively each of as many as 131 image features and then reported on each of the two differentiations. The diagnostic value of each feature was assessed, and linear discriminant analysis was used to develop statistical prediction rules (SPRs) for merging feature data into computerized "second opinions." For the two differentiations, accuracy (area under the receiver operating characteristic curve [Az]) was then determined for the radiologists' readings by themselves and for each of three SPRs. RESULTS: Thirty-seven candidate features had diagnostic value for each of the two differentiations (a slightly different feature set for each). Radiologists' performance at both differentiations was excellent (Az = 0.929 [benign vs malignant] and 0.926 [hepatocyte-containing vs non-hepatocyte-containing]). Performance of the SPR that operated on the features from all modalities together was better than that of radiologists (Az = 0.936 [benign vs malignant] and 0.951 [hepatocyte-containing vs non-hepatocyte-containing]), but this difference was of marginal statistical significance (P = .11). Contrast-enhanced MR imaging and contrast-enhanced CT each made significant adjunctive contributions to accuracy compared with unenhanced MR imaging alone. CONCLUSION: Many CT- and MR imaging-based features have diagnostic value in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Radiologists could also benefit from the fully informed SPR's "second opinions."

Adult↗
PubMedDate not supplied

Multimodality treatment for patients with hepatocellular carcinoma: analysis of prognostic factors in a single Western institution series.

There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including orthotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham from January 1990 through December 1999. Clinicopathologic and treatment factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or IV tumors. The median follow-up for survivors was 22 months. The 1-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial 1-, 3-, and 5-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.

Adolescent↗
PubMedDate not supplied

Tramadol and beta-cyclodextrin piroxicam: effective multimodal balanced analgesia for the intra- and postoperative period.

BACKGROUND AND OBJECTIVES: This study was conducted to evaluate the analgesic efficacy of tramadol, an analgesic with both opioid and nonopioid actions (norepinephrine and serotonin pathways), with beta-cyclodextrin piroxicam, a nonsteroidal antiinflammatory drug, in the perioperative setting. METHODS: The study population consisted of 48 patients scheduled for minor abdominal procedures, who were assigned to one of four groups of 12 patients each. The premedication was either a placebo tablet or a 192.1-mg beta-cyclodextrin piroxicam tablet, administered orally 30-40 minutes before anesthesia induction. After intravenous administration of tramadol 1.5 mg/kg, anesthesia was induced with an intravenous loading dose of propofol. Anesthesia was maintained an intravenous infusion of propofol at 6-12 mg/kg/h plus either saline or tramadol at 1.2 mg/kg/h, atracurium, and a 2:1 nitrous oxide-oxygen mixture. The control group received a placebo tablet and an infusion of saline with propofol for anesthesia maintenance; the tramadol group received a placebo tablet and a continuous tramadol-propofol infusion; the beta-cyclodextrin piroxicam (BCP) group received a BCP tablet and a continuous saline-propofol infusion; and the beta-cyclodextrin piroxicam-tramadol (BCPT) group received beta-cyclodextrin piroxicam and a continuous tramadol-propofol infusion. RESULTS: The relative propofol consumption by the four groups was control = BCP (P > .05) >tramadol (P < .001) > B-CPT (P < .0002). The time for analgesic rescue decreased in the order BCPT > BCP (P < .0002) = tramadol > control (P < .001). The degree of sedation and the visual analog scores 10-cm scale at the time patients requested rescue analgesics were similar among the groups (P > .05). CONCLUSIONS: The combination of tramadol and beta-cyclodextrin piroxicam provided better perioperative analgesia than tramadol alone.

Abdomen↗
PubMed2001

[Physical and methodological aspects of multimodality imaging and principles of treatment planning in 3D conformal radiotherapy].

The recent evolutions of the imaging modalities, the dose calculation models, the linear accelerators and the portal imaging permit to improve the quality of the conformal radiation therapy treatment planning. With DICOM protocols, the acquired imaging data coming from different modalities are treated by performant image fusion algorithms and yield more precise target volumes and organs at risk. The transformation of the clinical target volumes (CTV) to planning target volumes (PTV) can be realised using advanced probabilistic techniques based on clinical experience. The treatment plans evaluation is based on the dose volume histograms. Their precision and clinical relevance are improved by the multi-modality imaging and the advanced dose calculation models. The introduction of the inverse planning systems permitting to realise modulated intensity radiation therapy generates highly conformal dose distributions. All the previously cited complex techniques require the application of rigorous quality assurance programs.

Dose Fractionation, Radiation↗
PubMed2001

Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal electrophysiological study.

OBJECTIVE: To evaluate the effects of mechanical compression of the brain-stem in patients with vertebrobasilar dolichoectasia (VBD). METHODS: In the framework of a prospective, observational study that collected clinical and laboratory data in patients with VBD, we studied 20 patients with compression of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral lesions other than small lacunae in the white matter of the cerebral hemispheres were excluded from the study. Patients underwent vestibular and auditory function testing, including brain-stem auditory evoked potentials (BAEPs), blink reflex (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs). RESULTS: Almost all of the patients complained of auditory or vestibular symptoms and none had symptoms or signs of impairment of long tracts or the facial and trigeminal nerves. The most consistent findings were BR abnormalities with prolongation of ipsilateral R1 latency in cases of compression of the pons (10/16) and prolongation of the R2 and R2c latencies with compression of the medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was found in 13 out of 25 instances of compression, and this was more frequent with compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered, and only in cases with compression of the pons. CONCLUSIONS: Neurovascular compression of the brain-stem, even with severe distortion, is seldom associated with overt clinical signs, whereas subclinical dysfunctions are relatively frequent. The central pathways of the BR and the corticospinal pathways are more susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP data provide a functional evaluation of the brain-stem and some cranial nerves, which is lacking in imaging studies. Functional investigations may be useful in the long-term management of these patients, since VBD may be progressive and surgical correction may be required at some stage.

Adult↗
PubMed2003

The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A).

OBJECTIVES: Biological markers of narcolepsy with cataplexy (classical narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF) hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF leptin. The clinical borderland of narcolepsy and the diagnostic value of different markers of narcolepsy remain controversial and were assessed in a consecutive series of 27 patients with hypersomnia of (mainly) neurological origin. METHODS: Diagnoses included classical narcolepsy (n=3), symptomatic narcolepsy (n=1), narcolepsy without cataplexy (n=4), idiopathic hypersomnia (n=5), hypersomnia associated with psychiatric disorders (n=5), and hypersomnia secondary to neurological disorders or of undetermined origin (n=9). Clinical assessment included BMI, Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy Scale (UNS), and history of REM-symptoms (sleep paralysis, hallucinations). HLA-typing, electrophysiological studies (conventional polysomnography, MSLT, 1-week actigraphy), and measurements of CSF levels of hypocretin and leptin were also performed. RESULTS: Hypocretin-1 was undetectable in three patients with classic narcolepsy and detectable in the remaining 24 patients. Other narcoleptic markers also frequently found in patients without narcolepsy included ESS>14 (78% of 27 patients), UNS>14 (75%), REM symptoms (30%), sleep latencies on MSLT<5 min (41%), >/=2 SOREM (30%), DQB1*0602 positivity (52%), BMI>25 (52%), and increased CSF leptin (48%). Hypersomnia was documented by an increased time 'asleep' in 41% of patients. Overlapping clinical and electrophysiological findings were seen mostly in patients with narcolepsy without cataplexy, idiopathic hypersomnia, and psychiatric hypersomnia. CONCLUSIONS: (1) Hypocretin dysfunction is not the 'final common pathway' in the pathophysiology of most hypersomnolent syndromes that fall on the borderline for a diagnosis of narcolepsy. (2) The observed overlap among these hypersomnolent syndromes implies that current diagnostic categories are not entirely unambiguous. (3) A common hypothalamic, hypocretin-independent dysfunction may be present in some of these syndromes.

Adolescent↗