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PubMed2003

[Evaluation of conservative combined modality therapy of lumbar radicular pain syndrome].

OBJECTIVE: In this summary, the preliminary results of studies evaluating medical therapy of radicular low back pain are reported. METHODS: In two prospective cohorts (183 patients) the conservative multimodal inpatient treatment was examined, using the newly developed "Radicular Low Back Pain Score" for the standardized measurement of the radiculopathy. In another sample of 116 patients the preceding outpatient treatment was documented. RESULTS: A significant short-term improvement with regard to the pain intensity and the radiculopathy was observed after approximately two weeks of therapy. The preceding outpatient treatment did not comply with recent guidelines. Moreover, it did not influence the outcome of the multimodal inpatient therapy. CONCLUSIONS: The "Radicular Low Back Pain Score" seems to be a suitable instrument for measuring therapy effectiveness. Multimodal medical treatment is an important treatment approach for sciatica, especially after failed outpatient therapy.

Ambulatory Care↗

PubMedDate not supplied

Primary intestinal lymphoma: clinical and therapeutic features of 32 patients.

BACKGROUND AND OBJECTIVE: Lymphomas of the gastrointestinal tract are the most common type of primary extranodal lymphomas, accounting for 5 to 10% of all non-Hodgkin's lymphomas. In particular, primary intestinal lymphomas represent about 15-20% of gastrointestinal lymphomas. New multimodal therapeutic approaches have improved the prognosis of this once deadly disease: we report a retrospective analysis of our experience with 32 cases of primary western intestinal lymphomas, presenting clinical, therapeutical and prognostic data. PATIENTS AND METHODS: From March 1989 to November 1995, 32 patients with untreated primary western intestinal lymphomas were submitted to radical surgery plus polychemotherapy (early stages, I and II; 22 patients), or polychemotherapy alone (advanced stage, III and IV; 10 patients). The most frequent symptoms were abdominal pain, nausea, vomiting and weight loss. The tumor was located in the jejunum in 2 cases (6.2%), in the proximal small bowel in 15 cases (46.9%), in the distal and terminal ileum in 8 cases (25%), in the colon and rectum in 4 cases (12.5%), and multiple sites were found in 3 cases (9.4%). According to histology, 26 patients had high-grade and 6 low-grade non-Hodgkin's lymphoma. RESULTS: Stage I-II patients underwent radical resection of the tumor and chemotherapy; advanced (III-IV) stage patients were treated with chemotherapy alone as first-line approach. Of the 32 patients, 24 (75%) achieved a complete response (CR); according to stage, all stage I-II patients had CR, while only 2 of the 10 stage III-IV patients reached CR. The risk of a lower response rate was significantly correlated with the presence of advanced stage (III-IV) (p = 0.000001). The overall 5-year survival rate was 59%, with a relapse-free survival rate of 72% among the 24 complete responders. INTERPRETATION AND CONCLUSIONS: Intestinal lymphomas differ significantly from their gastric counterpart, not only in pathology, but also with regard to clinical features, management and prognosis. Our experience confirm the efficacy of the surgery-chemotherapy combination in obtaining a good remission rate for localized early primary intestinal lymphoma and indicates that this combination represents the only means for managing complications.

Adolescent↗

PubMed2023

Inferring Metabolic States from Single Cell Transcriptomic Data via Geometric Deep Learning.

The ability to measure gene expression at single-cell resolution has elevated our understanding of how biological features emerge from complex and interdependent networks at molecular, cellular, and tissue scales. As technologies have evolved that complement scRNAseq measurements with things like single-cell proteomic, epigenomic, and genomic information, it becomes increasingly apparent how much biology exists as a product of multimodal regulation. Biological processes such as transcription, translation, and post-translational or epigenetic modification impose both energetic and specific molecular demands on a cell and are therefore implicitly constrained by the metabolic state of the cell. While metabolomics is crucial for defining a holistic model of any biological process, the chemical heterogeneity of the metabolome makes it particularly difficult to measure, and technologies capable of doing this at single-cell resolution are far behind other multiomics modalities. To address these challenges, we present GEFMAP (Gene Expression-based Flux Mapping and Metabolic Pathway Prediction), a method based on geometric deep learning for predicting flux through reactions in a global metabolic network using transcriptomics data, which we ultimately apply to scRNAseq. GEFMAP leverages the natural graph structure of metabolic networks to learn both a biological objective for each cell and estimate a mass-balanced relative flux rate for each reaction in each cell using novel deep learning models.

Preprint↗

PubMed2003

Multimodality imaging for precise localization of craniofacial osteomyelitis.

Functional imaging identifies areas of abnormal bone turnover, providing a useful adjunct in the treatment of osteomyelitis and bone tumors. The low resolution and lack of anatomical detail limit the application of bone scans in craniofacial surgery, however. Multimodality image registration addresses this problem by fusing functional images (single photon emission computed tomography [SPECT]) to high-resolution structural images (computed tomography [CT]) for precise anatomical delineation of bone activity. This article describes a technique for spatial registration of CT and SPECT images to provide precise anatomical delineation of abnormal bone turnover, thereby guiding the extent of resection in the management of craniofacial osteomyelitis. Standard CT and SPECT imaging protocols were used in imaging the skull from the vertex to the mentum. Image data were imported into Analyze (Biomedical Imaging Resource; Mayo Foundation, Rochester, MN) on a dedicated Windows NT (Microsoft Corporation, Redmond, WA) workstation. Using the CT data, the craniofacial skeleton, osteotomy segments, and bone grafts were interactively mapped out. Consecutive axial slices were then reconstructed to form a three-dimensional volume of interest. The CT-derived volume of interest was registered to the technetium Tc 99m-methylene diphosphonate SPECT scan using the Analyze program to provide a fused multimodality image. The imaging technique was used to localize osteomyelitis in a complex craniofacial reconstruction. The fused images guided the extent of resection during surgery, and postoperative microbiological and histological testing confirmed the diagnosis. Multimodality image registration provides a readily available method to relate facial skeletal anatomy and physiology. This technique is valuable in planning and monitoring therapeutic interventions in clinical conditions in which bone turnover is abnormal.

Adult↗

PubMed2003

Model of surgical procedures for multimodal image-guided neurosurgery.

OBJECTIVE: Improvement of the planning stage of image-guided surgery requires a better anticipation of the surgical procedure and its anatomical and functional environment. This anticipation should be provided by acquisition of multimodal medical images of the patient and by a better understanding of surgical procedures. In this paper, we propose improvements to the planning and performance of multimodal image-guided neurosurgery through the use of information models related to neurosurgical procedures. MATERIALS AND METHODS: A new generic model of surgical procedures is introduced in the context of multimodal image-guided craniotomies. The basic principle of the model is to break down the surgical procedure into a sequence of steps defining the surgical script. In the model, a step is defined by an action. The model assigns to each surgical step a list of image entities extracted from multimodal preoperative images (i.e., anatomical and/or functional images) which are relevant to the performance of that particular step. A semantic validation of the model was performed by instantiating the model entities for 29 surgical procedures. RESULTS: The resulting generic model is described by a UML class diagram and a textual description. The validation showed the relevance of the model, confirming the main underlying assumptions. It also provided some leads to improve the model. CONCLUSION: While further validation is needed, the initial benefits of this approach can already be outlined. It should add real value to the different levels of image-guided surgery, from preprocessing to planning, as well as during surgery. Models of surgical procedures can manage image data according to the surgical script, which should lead to better anticipation of surgery through the development of simulation tools. Furthermore, the models may improve the performance of surgery using microscope-based neuronavigation systems by making it possible to adapt both visualization and interaction features of multimodal preoperative images according to the model.

Humans↗

PubMed2004

'Fast-track' multimodal rehabilitation program improves outcome after laparoscopic sigmoidectomy: a controlled prospective evaluation.

BACKGROUND: Laparoscopic colorectal resection improves patient outcome by reducing pain, postoperative pulmonary dysfunction, gastrointestinal paralysis, and fatigue. A multimodal rehabilitation program ("fast-track") with epidural analgesia, early oral feeding, and enforced mobilization may further improve the excellent results of laparoscopic colorectal resection, enabling early ambulation of these patients. METHODS: Fifty two consecutive patients underwent laparoscopic sigmoidectomy with standardized regular perioperative treatment (standard) or multimodal rehabilitation program ("fast-track"). Outcome measures included pulmonary function, duration of postoperative ileus, pain perception, fatigue, morbidity, and mortality. RESULTS: Twenty nine standard-care patients (19 men and 10 women) and 23 fast-track patients (15 men and eight women) were evaluated. Demographic and operative data were similar for the two groups. On the 1st postoperative day, pulmonary function was improved (p = 0.01) in fast-track patients. Oral feeding was achieved earlier (p < 0.01) and defecation occurred earlier (p < 0.01) in the fast-track group. Visual analogue scale scores for pain were similar for the two groups (p > 0.05), but fatigue was increased in the standard-care group on the 1st (p = 0.06) and 2nd (p < 0.05) postoperative days. Morbidity was not different for the two groups. Fast-track patients were discharged on day 4 (range, 3-6) and standard-care patients on day 7 (range, 4-14) (p < 0.001). CONCLUSION: Multimodal rehabilitation can improve further on the excellent results of laparoscopic sigmoidectomy and decrease the postoperative hospital stay.

Adult↗

PubMed2026

EGFLAM Pathogenic Variants and Congenital Stationary Night Blindness.

IMPORTANCE: Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous inherited retinal disorder (IRD), and in many complete CSNB (cCSNB) cases, the underlying genetic cause remains unknown. Uncovering the genetic defects of IRDs helps to refine diagnostic methods and supports the development of specific therapeutic approaches. OBJECTIVE: To describe the phenotype and the underlying gene defect in patients with cCSNB from 2 unrelated families. DESIGN, SETTING AND PARTICIPANTS: This retrospective case series was conducted from January 2023 to July 2025. Data for 3 patients from cohorts of genetically unsolved IRD cases in France (n = 140 for CSNB) and the Netherlands (n = 2730 for IRD) were analyzed clinically and genetically. EXPOSURES: Complete ocular examination, including multimodal retinal imaging and full-field electroretinography (ffERG) incorporating the International Society for Clinical Electrophysiology of Vision standards and multimodal retinal imaging, were performed. Gene defects were identified by genome sequencing (GS) and exome sequencing (ES). MAIN OUTCOMES AND MEASURES: The main outcome was a gene defect, EGFLAM, underlying cCSNB. Measures included phenotyping, GS, ES, Sanger sequencing, and cosegregation analysis. RESULTS: The series included 3 patients from 2 unrelated families of Moroccan ancestry showing high myopia, reduced visual acuity, and night blindness. Retinal imaging depicted myopic changes. ffERG revealed electronegative Schubert-Bornschein configuration in keeping with cCSNB with ON-bipolar cell dysfunction. Patients were lacking pathogenic variants in known genes implicated in IRDs, including CSNB. Two different homozygous pathogenic variants, c.1563_1566del, p.(Val522Glufs*18) and c.1795C>T, p.(Arg599*) in EGFLAM were identified by ES and GS. The corresponding protein is localized in the outer plexiform layer and important for ON-bipolar cell signaling in the retina. CONCLUSION AND RELEVANCE: This case series reports on a gene defect in EGFLAM implicated in human cCSNB. Clinicians should be aware about this association and consider including EGFLAM in diagnostic gene panels for IRDs. This discovery may lead to faster and more accurate diagnosis of cCSNB and genetic counseling, as well as a pathway for developing therapies.

Adolescent↗

PubMed1982

Analysis of neuronal soma size distributions.

Neuronal soma size distributions are often very skewed, leading to difficulty in their characterization and in the application of statistics commonly used to describe normally distributed variables. A particular family of curves, called Weibull functions, can be shown to fit cell size data extremely well. These functions not only characterize these skewed distributions, but do so in a way which permits powerful, sensitive comparisons of differences between distributions. Because of the flexibility of the Weibull functions, they may be used to describe a variety of morphological attributes. Several applications of these functions to neuroanatomical data are described using methods which require only graph paper and hand calculator for curve fitting. An extension of the basic curve fitting method permits mixtures of Weibull functions to be used in describing multimodal size histograms.

Animals↗

PubMed1989

Locally advanced breast cancer current status and future directions.

Patients described as having locally advanced breast cancer comprise a heterogeneous group of patients with variable clinical presentations. Systematic evaluation of patients with these presentations has been limited, with much of our current understanding based on retrospective reviews. Prospective pilot studies have demonstrated the feasibility of multimodality therapy. However, there have been few well-conducted randomized trials in this setting. Comparison of results among studies is made difficult by the varying eligibility criteria and the way in which the data are reported. The use of common and consistent definitions of operable and inoperable disease is necessary for a more uniform understanding of the therapeutic interventions necessary for a given patient within this broad category of Stage III or locally advanced breast cancer. There are a variety of opportunities for clinical research activities in this group of patients including tests of hormonal recruitment or synchronization, high dose chemotherapy requiring autologous bone marrow transplantation, perioperative or preoperative chemotherapy, and alternating chemotherapy with short course radiotherapy. The integration of clinical information with biological characteristics of the tumor such as cytokinetics, oncogene amplification, and hormone receptors will be an important and necessary focus of future investigation in this disease.

Breast Neoplasms↗

PubMed2026

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗

PubMed1993

Recovery of a temporally based visual discrimination after visual cortex lesion in the rat.

In Expt. 1, rats were conditioned to emit a shock avoidance response when the pulse rate of a light was increased. Then, after bilateral visual cortex lesions, the rats were given 10, 20, or 40 days recovery before relearning the discrimination. While all rats were able to relearn the discrimination response, lesion rats had a performance deficit after all recovery periods. Expt. 2 compared the effects of postoperative visual pulse rate training to those of auditory pulse rate training on relearning of the photic pulse-rate discrimination 10 days after visual decortication. Recovery of discrimination responding was better after auditory pulse rate training than after visual training. These data suggest that visual cortex lesions in the rat disrupt perceptual or associational functions involving the temporal features of a visual stimulus. In addition, generalization of relational properties during cross-modal training through multimodal CNS structures appears to enhance recovery of behavior after brain insult.

Acoustic Stimulation↗

PubMed2002

Dichotic listening in patients with splenial and nonsplenial callosal lesions.

The authors found splenial lesions to be associated with left ear suppression in dichotic listening of consonant-vowel syllables. This was found in both a rapid presentation dichotic monitoring task and a standard dichotic listening task, ruling out attentional limitations in the processing of high stimulus loads as a confounding factor. Moreover, directed attention to the left ear did not improve left ear target detection in the patients, independent of callosal lesion location. The authors' data may indicate that auditory callosal fibers pass through the splenium more posterior than previously thought. However, further studies should investigate whether callosal fibers between primary and secondary auditory cortices, or between higher level multimodal cortices, are vital for the detection of left ear targets in dichotic listening.

Adult↗

PubMed1999

Manic-depression neural conduction speeds and action potential event dyscorrelation.

In manic-depressive disorder, the monotonic, humor/receptor, excess/deficit, i.e. gain, theories have prevailed for many years, even though there is increasing evidence of a timing abnormality that may or may not be related to gain. In addition, the manic-depressive course is clearly multimodal and unpredictable except in revealing but rare cases, yet the system is real, and thus presumably deterministic, clearly suggesting a dynamic instability. A wide range of disciplines was reviewed by the author. Those data that were significantly different by standard tests were considered. However, averaged values were always questioned. During this review, higher water compartmentalization differentials were found in manic-depressive patients. Also indicated, event-related potential components differed in latency correlations, suggesting action potential firing event dyscorrelation. In conclusion, the manic-depressive action potential firing events may be dyscorrelated in a space-time reference frame.

Action Potentials↗

PubMed2005

Effects of combined treatment on Turkish children diagnosed with attention-deficit/hyperactivity disorder: a preliminary report.

OBJECTIVE: The main aim of this study was to investigate the effects of combined treatment on children diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHOD: After careful screening, 47 children (57%) diagnosed with ADHD + oppositional defiant disorder (ODD) and 36 children (43%) diagnosed with ADHD + conduct disorder (CD) were included in the study. Treatment consisted of ongoing medication (methylphenidate) management and a parent-training program that continued for 5 months. Children were assessed in multiple domains by multiple sources of information at baseline and at the end of the 1st, 3rd, and 6th months by parent- and teacher-completed the Turgay Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S), Conners Parent Rating Scale (CPRS), and Conners Teacher Rating Scale (CTRS). Mother-child relationship was assessed by the Parental Acceptance and Rejection Questionnaire (PARQ). RESULTS: Combined treatment was effective in reducing the ADHD, ODD, and CD symptoms. Analyses of the data revealed that medication, rather than parent training, was responsible for the improvements both in the symptoms and in the mother-child relationship. CONCLUSIONS: The results of the study, in line with the Multimodal Treatment Study of Children with ADHD (MTA) findings, highlighted the role of stimulant medication in the treatment of ADHD.

Adolescent↗

PubMed1998

Estimation for restriction sites observed by optical mapping using reversible-jump Markov Chain Monte Carlo.

A fundamentally new molecular-biology approach in constructing restriction maps, Optical Mapping, has been developed by Schwartz et al. (1993). Using this method restriction maps are constructed by measuring the relevant fluorescence intensity and length measurements. However, it is difficult to directly estimate the restriction site locations of single DNA molecules based on these optical mapping data because of the precision of length measurements and the unknown number of true restriction sites in the data. We propose the use of a hierarchical Bayes model based on a mixture model with normals and random noise. In this model we explicitly consider the missing observation structure of the data, such as the orientations of molecules, the allocations of cutting sites to restriction sites, and the indicator variables of whether observed cut sites are true or false. Because of the complexity of the model, the large number of missing data, and the unknown number of restriction sites, we use Reversible-Jump Markov Chain Monte Carlo (MCMC) to estimate the number and the locations of the restriction sites. Since there exists a high multimodality due to unknown orientations of molecules, we also use a combination of our MCMC approach and the flipping algorithm suggested by Dancík and Waterman (1997). The study is highly computer-intensive and the development of an efficient algorithm is required.

Algorithms↗

PubMed1991

Computer applications in radiology.

Computer applications in radiology are evolving rapidly, tied to incremental improvements in hardware, software, and methods. In computer hardware, the emergence of dramatically improved graphic and computational performance for engineering workstations enables their use for visualization. Major changes in networking, storage, and display technology play a major role in influencing applications. The use of three-dimensional digitizers to perform localization of real three-dimensional points in conjunction with images and the rendering of objects using rapid prototyping methods, such as stereolithography, were recently reported. Major software advances have taken place through the availability of applications packages that are operated with menu-driven or point-and-click user interfaces, data flow languages, or complete turnkey applications. Imaging methods including CT, MR imaging, digital radiography, biomagnetism, and optical range sensing, which take advantage of advanced computer technology, are new this year. Image processing for multimodality fusion or image registration, visualization, reconstruction, and quantification of images, have been reported at a wide variety of conferences and in key publications. New computer methods to fabricate custom orthopaedic implants, and to improve imaging technology assessment were introduced.

Brain↗

PubMedDate not supplied

Multimode ligand binding in receptor site modeling: implementation in CoMFA.

Receptor site modeling methods usually use one binding mode (conformation and/or orientation) for each ligand in a 1:1 complex with receptor. Multiple modes should be considered instead because (1). they have frequently been observed experimentally; (2). in a series, ligands can bind in single yet different modes; and (3). a series may only exhibit one but unknown mode and a few plausible modes must be examined. For multimode binding, the observed ligand/receptor association constant is the sum of the association constants that characterize individual binding modes. This relation, when applied to Comparative Molecular Field Analysis (CoMFA), results in a dependence of the observed binding energy on the probe energies that is nonlinear in optimized parameters. The dependence was linearized to allow parameter optimization by the partial least-squares method that was used iteratively until self-consistency. In addition to the standard CoMFA output, the procedure objectively selects one or a few optimal binding modes out of a dozen or more modes that are considered for each ligand. The approach was applied to published data for binding of 34 polychlorinated dibenzofurans to the aryl hydrocarbon receptor. Descriptive and predictive abilities of the 16-mode model were significantly better than for the one-, two-, and four-mode models. Predominantly, edge-aligned modes were selected that are seldom used in CoMFA. Since inclusion of multimode binding only changes the form of the correlation equation and does not affect the number of optimized parameters, the improvement is believed to be due to a more realistic description.

Algorithms↗

PubMed2004

Bronchoscopic palliation of primary lung cancer: single or multimodality therapy?

BACKGROUND: An obstructing primary lung cancer is a challenging disease frequently requiring endobronchial interventional therapy. A variety of interventional modalities, including Nd:YAG laser, stenting, photodynamic therapy (PDT), and endoluminal brachytherapy, are utilized to relieve airway obstruction and bleeding. The aim of this study is to compare the effect on patient survival of bronchoscopic palliation for lung cancer utilizing one interventional modality compared to the use of combination of modalities to relieve the airway problem. METHODS. We reviewed our longitudinal experience with interventional bronchoscopy in 75 patients who underwent 176 procedures for the management of endobronchial lung cancer between 1994 and 2002. Indication for intervention was hemoptysis in 24 patients (32%) and airway obstruction in the remaining. Six patients died within 30 days from the first intervention and were excluded. Forty of the surviving 69 patients (58%) were treated with a single interventional modality (group A). In 29 patients (42%) a multimodality endoscopic treatment was utilized (group B). Single-modality treatment in group A included Nd-YAG laser in 60%, stent in 17%, brachytherapy in 20%, and PDT in 3%. A variety of combinations of the aforementioned modalities were used in group B to enhance airway patency. Patient data were compared with the Student's t-test and chi-square test. Survival analysis and the log rank test were used to compare difference in survival between the two groups. A p-value of 0.05 was considered significant. RESULTS: There were 46 males and 23 females, with a mean age of 67 years. The tumor was located in the trachea 9%, in the carina in 7%, and primary bronchial in 84%. Two patients had complications due to stent malposition. There was no significant difference between the two groups in relation to age, gender, tumor location, histology, and type of previous cancer therapy. There was a significant improvement in survival for the multimodality group (p = 0.04). The 1- and 3-year cumulative survival rate for groups A and B was 51.3% versus 50% and 2.3% versus 22%, respectively. CONCLUSIONS: Improvement in survival can be seen with diligent airway surveillance after interventional bronchoscopy and liberal use of a variety of endobronchial treatment modalities for airway obstruction or bleeding. Physicians involved in the management of this difficult problem should be versed in the use of all available treatment modalities to enhance therapeutic outcome.

Aged↗