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PubMed1988

Multimodal evoked potential studies in leukodystrophies of children.

Evoked potentials were studied in 22 children with leukodystrophy [10 metachromatic leukodystrophy (MLD), 4 Pelizaeus-Merzbacher (PM), 3 Krabbes, 2 adrenoleukodystrophy (ALD), and one each of Alexander's, Canavan's and multiple sulphatase deficiency (MSD) diseases]. The ABRs were abnormal in all patients (except for the younger ALD), but varied with the type of leukodystrophy. The PM and Krabbes patients had abnormal ABRs with a loss of the rostral waves, accompanied in Krabbes with delayed I-III interpeak latencies; in MLD, ALD and MSD prolonged interpeak latencies were found. Three patients who had no clinical signs, but were positively diagnosed as MLD on the basis of absent arylsulphatase A, also had abnormal ABRs. The SEPs were abnormal in all patients. Cortical SEPs were absent in 16 and abnormal in 5 who were in the earlier stages of their disease. Cervical SEPs were within normal limits except for the Krabbes and MLD patients studied, who showed peripheral slowing. The VEPs were normal in only 6 and, unlike the ARBs and SEPs, did not seem to covary with clinical severity across the various leukodystrophies but did correlate with disease progression. Thus, multimodal EPs are useful in the diagnostic differentiation of the leukodystrophies.

Adolescent↗
PubMed1998

Near-ultraviolet evanescent-wave absorption sensor based on a multimode optical fiber.

Fiber-optic near-ultraviolet evanescent-wave sensors have been constructed, and their feasibility for practical applications has been demonstrated. The sensors, used for the detection of ozone near the 254-nm peak of the Hartley absorption band, were fabricated from coiled segments of low-cost multimode plastic-clad silica optical fibers. The sensing sections were produced alternatively by stripping only the protective jacket from the fiber to expose the gas-permeable silicone cladding or by stripping the jacket and the cladding to expose the bare-silica fiber core. Response characteristics are given, including sensitivity to ozone, reversibility, and aging effects. The useful lifetime was unacceptably short for the sensor that employed the bare-silica core, whereas the exposed-cladding sensor demonstrated good stability over the entire two-month period of investigation. The latter, more useful sensor demonstrated a linear response to ozone over the range 0.02-0.35 vol% and a reversible response with a time constant on the order of 1 min. Differences in ozone absorption spectra obtained in the transmission and evanescent-wave modes are discussed. Projected applications of the new exposed-cladding sensor include ozone determination in water-treatment processes and ozone production plants.

Absorption↗
PubMedDate not supplied

Multimodality in vivo molecular-genetic imaging.

Multimodality imaging is increasingly being used in molecular-genetic studies in small animals. The coupling of nuclear and optical reporter genes represents the beginning of a far wider application of this technology. Optical imaging and optical reporter systems are cost-effective and time-efficient, they require less resources and space than PET or MRI, and they are particularly well suited for small animal imaging and for in vitro assays to validate different reporter systems. However, optical imaging techniques are limited by depth of light penetration and scatter and do not yet provide optimal quantitative or tomographic information. These issues are not limiting for PET- or MRI-based reporter systems, and PET- and MRI-based animal studies are more easily generalized to human applications. Many of the shortcomings of each modality alone can be overcome by the use of dual- or triple-modality reporter constructs that incorporate the opportunity for PET, fluorescence and bioluminescence imaging. We optimistically expect that some form of tomographic, small animal optical imaging capability will be developed soon, and that this will provide the opportunity for the colocalization of optical signals to anatomical structures provided by tomographic CT and MR imaging.

Animals↗
PubMedDate not supplied

Monomolecular multimodal fluorescence-radioisotope imaging agents.

Diagnosis of diseases by different imaging methods can provide complementary information about the functional status of diseased tissues or organs. To overcome the current difficulties in coregistering images from different imaging modalities with a high degree of accuracy, we prepared near-infrared (NIR) monomolecular multimodal imaging agents (MOMIAs) consisting of a heptamethine carbocyanine and 111In-DOTA chelate that served as antennae for optical and scintigraphic imaging, respectively. Their spectral properties clearly show that coordination of indium to MOMIA increased the fluorescence intensity of the compounds. The MOMIAs are exceptionally stable in biological media and serum up to 24 h at 37 degrees C. Biodistribution of the compounds in mice obtained by fluorescence photon and gamma-counts demonstrated a similar distribution trend of the molecular probe in different tissues, suggesting that the detected fluorescence and gamma-emissions emanated from the same source (MOMIA). At 24 h postinjection, the MOMIAs were excreted by the renal and hepatobiliary systems and the blood level of a representative MOMIA was very low, thereby reducing background noise caused by circulating molecular probes. These findings demonstrate the feasibility of preparing single molecules with the capacity to emit discernible and diagnostic fluorescent and gamma-radiations for optical and nuclear imaging of living organisms.

Animals↗
PubMed2006

Nanoscale metal-organic frameworks as potential multimodal contrast enhancing agents.

Nanoscale metal-organic frameworks (NMOFs) based on Gd3+ centers and benzenedicarboxylate and benzenetricarboxylate bridging ligands were synthesized using reverse microemulsions and characterized using SEM, PXRD, and TGA. These NMOFs exhibit extraordinarily large R1 and R2 relaxivities because of the presence of up to tens of millions of Gd3+ centers in each nanoparticle and are thus efficient T1 and T2 contrast agents for MRI. The NMOFs can also be made highly luminescent by doping with Eu3+ or Tb3+ centers. The results from this work suggest that NMOFs can be used as potential contrast agents for multimodal imaging.

Contrast Media↗
PubMed2005

Multimodality agents for tumor imaging (PET, fluorescence) and photodynamic therapy. A possible "see and treat" approach.

Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2), obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative), was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT). The electrophilic aromatic iodination of the corresponding trimethylstannyl intermediate with Na124I in the presence of an Iodogen bead afforded 124I-labeled photosensitizer 4 with >95% radioactive specificity. In addition to drug-uptake, the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure. The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (lambda(max) 665 nm) at 24 h postinjection. The photosensitizer also showed promising tumor fluorescence and PET imaging ability. Our present work demonstrates the utility of the first 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.

Animals↗
PubMed2006

Protein interactions with self-assembled monolayers presenting multimodal ligands: a surface plasmon resonance study.

This paper describes the use of surface plasmon resonance (SPR) spectroscopy and self-assembled monolayers (SAMs) to understand the characteristics of surfaces that promote the adsorption of proteins at high ionic strengths (high-salt conditions). We synthesized SAMs presenting different multimodal ligands and determined the influence of surface composition, solution composition, and the nature of the protein on the extent of protein adsorption onto the SAMs. Our results confirm that hydrophobic interactions can contribute significantly to protein adsorption under high-salt conditions. In particular, the extent of protein adsorption under high-salt conditions increased with increasing surface hydrophobicity. The extent of protein adsorption was also influenced by the solution composition and decreased with an increase in the chaotropicity of the anion. The combination of SPR and SAMs is well-suited for studying the interaction of proteins with complex surfaces of relevance to chromatography.

Adsorption↗
PubMed2000

Commentary on the multimodal treatment study of children with ADHD.

The multimodal treatment study of attention deficit hyperactivity disorder (MTA Study) constitutes a landmark in the history of treatment research in child psychopathology, being the largest single study of its kind ever undertaken. Important findings have emerged from this project, as the papers in the present volume will attest. This commentary focuses on several concerns about the assumptions that appear to have guided the design of the MTA study, particularly its psychosocial treatment component, as well as the manner in which treatment results have been presented to date. In particular, no explicit theory of ADHD appears to have guided the construction of the treatment components, relying instead on implicit theories associated with those treatments, such as the notion that the symptoms of ADHD arise through faulty learning and defective contingencies of reinforcement. Future articles from this study will need to address these and other concerns if the results of the study are to be properly interpreted and the scientific and clinical yield is to be maximized.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Anxiety as a predictor and outcome variable in the multimodal treatment study of children with ADHD (MTA).

Initial moderator analyses in the Multimodal Treatment Study of Children with ADHD (MTA) suggested that child anxiety ascertained by parent report on the Diagnostic Interview Schedule for Children 2.3 (DISC Anxiety) differentially moderated the outcome of treatment. Left unanswered were questions regarding the nature of DISC Anxiety, the impact of comorbid conduct problems on the moderating effect of DISC Anxiety, and the clinical significance of DISC Anxiety as a moderator of treatment outcome. Thirty-three percent of MTA subjects met DSM-III-R criteria for an anxiety disorder excluding simple phobias. Of these, two-thirds also met DSM-III-R criteria for comorbid oppositional-defiant or conduct disorder whereas one-third did not, yielding an odds ratio of approximately two for DISC Anxiety, given conduct problems. In this context, exploratory analyses of baseline data suggest that DISC Anxiety may reflect parental attributions regarding child negative affectivity and associated behavior problems (unlike fearfulness), particularly in the area of social interactions, another core component of anxiety that is more typically associated with phobic symptoms. Analyses using hierarchical linear modeling (HLM) indicate that the moderating effect of DISC Anxiety continues to favor the inclusion of psychosocial treatment for anxious ADHD children irrespective of the presence or absence of comorbid conduct problems. This effect, which is clinically meaningful, is confined primarily to parent-reported outcomes involving disruptive behavior, internalizing symptoms, and inattention; and is generally stronger for combined than unimodal treatment. Contravening earlier studies, no adverse effect of anxiety on medication response for core ADHD or other outcomes in anxious or nonanxious ADHD children was demonstrated. When treating ADHD, it is important to search for comorbid anxiety and negative affectivity and to adjust treatment strategies accordingly.

Anxiety↗
PubMed1999

Prognostic factors and treatment-related changes associated with return to work in the multimodal treatment of chronic back pain.

The goals of the current study were to determine those preprogram (= prognostic) variables and treatment-related changes that predict return to work in the multimodal management of chronic back pain. The outcome measures for 143 patients at 6-month follow-up were analyzed. The program had a duration of 4 weeks, was based largely on the functional restoration approach (Mayer and Gatchel, 1998), and occurred within a workers' compensation framework. Some 87% of the patients successfully returned to work. Three sets of predictor variables were considered: demographic/socioeconomic data, physical measures, and psychological measures. Three prognostic variables proved to be significant negative predictors of return to work: time off work, previous spinal surgery, and a clinically elevated (preprogram) score on the MMPI-2 scale Lassitude-Malaise (Hy3). A repeated-measures MANOVA showed an incomplete return to work to be associated with only limited improvement in self-reported disability and pain report. However, patients who failed to return to work did not differ with regard to improvement in objective physical functioning or psychological distress. It is therefore hypothesized that a change in the perceived disability status is the key element necessary to return patients with chronic back pain to work, although ongoing reinforcement schemes operative in the home/work environment may lead to a relapse in the posttreatment phase.

Adult↗
PubMed1997

A multimodal, second generation, posttraumatic stress disorder rehabilitation program.

Second Generation posttraumatic stress disorder (PTSD) treatment programs were recently proposed as one component of a model of treatment of chronic PTSD. While First Generation PTSD programs emphasized trauma work, Second Generation programs emphasize skills for the present/future ability to adapt within society. The present paper describes a functioning Second Generation PTSD treatment program for Vietnam combat veterans. The guiding principles underlying this multimodal and vocational rehabilitation program are outlined.

Adaptation, Psychological↗
PubMed2003

Mutual information-based multimodality registration of cardiac ultrasound and SPECT images: a preliminary investigation.

BACKGROUND: Ultrasound (US) and single photon emission computed tomography (SPECT) are the two most commonly prescribed procedures for diagnosing coronary artery disease (CAD). We have demonstrated the feasibility of multimodality registration of two-dimensional (2D) and three-dimensional (3D) cardiac US images with cardiac SPECT images with an aim to simultaneously present the complementary anatomical and perfusion information from the two modalities. We have also tested the clinicians' assessment of the clinical adequacy of the registered images. METHODS AND RESULTS: We have demonstrated temporal and spatial registration for nine sets of cardiac US and SPECT cine loops covering the entire cardiac cycle. Temporal alignment was performed by interpolation of existing SPECT images at cardiac phases corresponding to available US images. Spatial registration was performed in 3D image space using a mutual information-based approach. Experts from echocardiography and nuclear medicine determined the clinical utility of the registration by rating each registration on a scale of 1 to 5, a rating of 3 or above indicating clinical utility. 2DUS-SPECT registration (five cases) received an average rating of 4.2, whereas 3DUS-SPECT registration (four cases) received an average rating of 2.85. By one-sample t test, the overall evaluations (mean 3.58) were greater than the pre-specified clinical cut-off of 3 with p < 0.05, indicating likelihood of clinical utility. CONCLUSION: Our method demonstrates the feasibility of registering cardiac US and SPECT images in their present as well as possible future forms. Such registration has the potential to provide a more accurate and powerful tool for diagnosing CAD.

Clinical Protocols↗
PubMed2004

Maintenance therapy with 13-cis retinoid acid in high-grade glioma at complete response after first-line multimodal therapy--a phase-II study.

BACKGROUND: Approximately 5% of patients with malignant glioma achieve complete response (CR) after first-line combined modality treatment. Although these patients will invariably suffer from tumor recurrence, they usually do not receive any further treatment to maintain remission. According to in vitro and in vivo clinical studies, 13-cis retinoic acid (cRA) may be a promising agent for maintenance therapy in these patients. OBJECTIVE: We initiated a clinical study to evaluate the feasibility and toxicity of high-dose cRA as maintenance therapy in patients with high-grade glioma in complete remission after first-line multimodal treatment. METHODS: A prospective single-arm phase-II study in patients with CR after combined first-line therapy (neurosurgery, radio- and chemotherapy) was performed. Patients were treated with cRA at 60 mg/m2 BS from day 1 to 21 in four-weekly cycles with a dose escalation of up to 100 mg/m2 BS until tumor recurrence. Clinical controls were performed every 4 weeks, magnetic resonance imaging every 8 weeks. RESULTS: Twenty-three patients (10, grade IV; 13, grade III) were evaluable using an intention-to-treat analysis. Treatment was well tolerated for up to 149 weeks with moderate dermatological symptoms in all patients. No grade 4 toxicities were observed. Median time to progression was 41 weeks, median overall survival 74 weeks after inclusion in the protocol. DISCUSSION: There is an urgent need for strategies maintaining remission in patients with malignant glioma. Maintenance therapy with high-dose cRA is feasible and well tolerated over long periods of time. A controlled clinical trial to test the efficacy of cRA as a maintenance treatment in malignant glioma is warranted.

Adult↗
PubMed2002

Superior prolonged antiemetic prophylaxis with a four-drug multimodal regimen - comparison with propofol or placebo.

BACKGROUND: The purpose of this study was to compare the effects of a low-dose propofol infusion with a four-drug multimodal regimen for prophylaxis of postoperative nausea and vomiting (PONV). METHODS: : PONV was studied in two patient groups with a known high incidence. Through a stratified randomization, 60 patients undergoing breast surgery and 120 patients undergoing abdominal surgery were randomized to three groups of equal size: the propofol group (P), the multidrug group (M) and the control group (C). All patients received general anesthesia, induction with propofol and maintenance with sevoflurane. After induction, patients in the P group received a continuous infusion of propofol 1 mg/kg/h during the operation and the first 4 postoperative h. Patients in the M group received dexamethasone 4 mg and three antiemetics, ondansetron 4 mg, droperidol 1.25 mg and metoclopramide 10 mg i.v. In the control group no prophylaxis was given. Nausea and pain were evaluated by incidence and a visual analog scale (0-10 cm). All emetic episodes were noted by the staff during the first 4 h and by the patients during the next 20 h. RESULTS: The overall incidence of PONV during the first 24 h postoperatively was significantly lower in the M group (24%) than in the P group (49%) (P<0.01) or the C group (70%) (P<0.001). The incidence of PONV increased significantly both in patients undergoing breast surgery and abdominal surgery after termination of propofol. The number of patients who vomited was significantly lower in the M group, both in breast surgery patients (5%) and abdominal surgery patients (3%) compared to patients in the propofol groups (breast 16% NS; abdominal 29%, P<0.05) and in the control groups (breast 37%, P<0.01; abdominal 29%, P<0.01). CONCLUSION: The incidence of PONV is very high in patients undergoing breast and abdominal surgery. In the present study antiemetic prophylaxis with a combination of droperidol, ondansetron, metoclopramide and dexamethasone was more effective in preventing PONV, especially vomiting, than a postoperative low-dose infusion of propofol, which had a short lasting effect.

Abdomen↗
PubMed1991

Development of intersensory function: age-related differences in stimulus selection of multimodal compounds in rats as revealed by Pavlovian conditioning.

Preweanling and adult rats were exposed to Pavlovian stimulus pairings with lights, tones, and light-tone compounds as conditional stimuli (CSs). Tone intensity was varied. As was found in previous studies using flavor CSs, odor CSs, or both, in which significant overshadowing or potentiation occurred to an element of a compound, overshadowing was less likely and potentiation more likely for preweanlings than for adults. Several experiments supported the view that these effects reflect an age-related difference in the controlling properties of stimuli: Young rats are more disposed to encode multimodal compounds on the basis of amodal intensity, whereas their elders are more likely to encode modality-specific properties of light and sound. Differential reinforcement in the presence of lights, tones, and light-tone compounds made preweanlings' stimulus selection appear more adultlike and may be a cause of development of intersensory function.

Aging↗
PubMed2005

Multimodal homesickness prevention in boys spending 2 weeks at a residential summer camp.

Homesickness is the distress or impairment caused by an actual or anticipated separation from home. It is characterized by preoccupying thoughts of home and attachment objects. In its severe form, homesickness is subjectively distressing and has clinically significant cognitive, emotional, and behavioral sequelae. This study provided 75 boys who ranged in age from 8 to 16 years and who were 1st-year campers at an overnight summer camp with an inexpensive, multimodal homesickness prevention package. Results suggest that combining environmental information, psychoeducation, social support, explicit coping instruction, caregiver education, practice time away from home, and surrogate caregiver training can reduce homesickness and associated behavior problems. These data support the theory that novelty reduction, attitudinal shifts, preseparation coping enhancement, and supportive social environments diminish the negative emotional intensity of homesickness.

Adaptation, Psychological↗
PubMed2006

Treatment-related changes in objectively measured parenting behaviors in the multimodal treatment study of children with attention-deficit/hyperactivity disorder.

The present study examined treatment outcomes for objectively measured parenting behavior in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD). Five hundred seventy-nine ethnically and socioeconomically diverse children with ADHD-combined type (ages 7.0-9.9 years) and their parent(s) were recruited at 6 sites in the United States and Canada and randomly assigned to 1 of 4 treatment groups for 14 months of active intervention: medication management (MedMgt), intensive behavior therapy, combination of the 2 (Comb), or a community-treated comparison (CC). Baseline and posttreatment laboratory observations of parent-child interactions were coded by observers blind to treatment condition. Comb produced significantly greater improvements in constructive parenting than did MedMgt or CC, with effect sizes approaching medium for these contrasts. Treatment effects on child behaviors were not significant. The authors discuss the importance of changes in parenting behavior for families of children with ADHD and the need for reliable and objective measures in evaluating treatment outcome.

Adult↗
PubMed1997

Infants' perception of expressive behaviors: differentiation of multimodal information.

The literature on infants' perception of facial and vocal expressions, combined with data from studies on infant-directed speech, mother-infant interaction, and social referencing, supports the view that infants come to recognize the affective expressions of others through a perceptual differentiation process. Recognition of affective expressions changes from a reliance on multimodally presented information to the recognition of vocal expressions and then of facial expressions alone. Face or voice properties become differentiated and discriminated from the whole, standing for the entire emotional expression. Initially, infants detect information that potentially carries the meaning of emotional expressions; only later do infants discriminate and then recognize those expressions. The author reviews data supporting this view and draws parallels between the perceptions of affective expressions and of speech.

Emotions↗