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PubMed2006

A novel method for the 3-dimensional simulation of orthognathic surgery by using a multimodal image-fusion technique.

INTRODUCTION: The aim of this study was to establish a novel method for simulating orthognathic surgery in 3-dimensional (3D) space. METHODS: This system mainly consists of 6 procedures: (1) reconstruction of a virtual skull model (VS) from presurgical computed tomography scans; (2) reconstruction of virtual dentition models from 3D surface scanning of dental casts occluded at presurgical and postsurgical intercuspal positions (VD1 and VD2, respectively); (3) reconstruction of a preliminary fusion model of VS and VD1 by an initial intermodality registration; (4) reconstruction of another preliminary fusion model of VS, VD1, and VD2 by a second intramodality registration; (5) repositioning of bony segments by a third intramodality registration and reconstruction of final fusion models at presurgery and postsurgery; and (6) 3D analysis of the movement of bony segments. To test this system, 2 patients with severe skeletal deformities, who had undergone presurgical orthodontic treatment, were used as models. Registration accuracy was determined by the root mean squared distance between the corresponding fiducial markers in a set of 2 images. RESULTS AND CONCLUSIONS: The sum of the root mean squared error of the 3 registration processes was less than 0.4 mm in both patients. This simulation system could be used to precisely realize the presurgical and postsurgical occlusal relationships and craniofacial morphology of a patient with severe skeletal deformities, and to quantitatively describe the movement of a given anatomical point of bony segments. It is assumed that there could be significant benefits in sharing visual and quantitative 3D information from this simulation system among orthodontists and surgeons.

Adult↗
PubMedDate not supplied

Multimodal treatment of locally advanced cervical cancer.

BACKGROUND: Radiation therapy with concomitant chemotherapy is the standard treatment for locally advanced cervical cancer. In Mexico, most patients are still treated with radiation therapy alone. The aim of this work was to demonstrate that results obtained with combined treatments in the Mexican population are similar to those reported in the literature. METHODS: Survival was analyzed in three sequential phase II studies of combined treatment: neoadjuvant chemotherapy followed by surgery (NEOCT+Sx) -February to July 1999; concomitant chemoradiotherapy (CT/RT) -August to December 1999; and neoadjuvant chemotherapy followed by surgery plus adjuvant chemoradiotherapy (NEOCT+Sx+CT/RT) -December 2000 to June 2001. These results were compared with a historical control group treated with radiation therapy alone between September and December 1998. The Kaplan-Meier product-limit method, log-rank test and Cox proportional hazards model were used for analysis. RESULTS: Results showed that the three combined modalities significantly reduced the risk of death. Treatment with NEOCT+Sx reduced the risk to 0.452 (95% CI 0.246-0.830), p=0.010. The risk reduction with CT/RT was 0.408 (95% CI 0.218-0.762), p=0.005, and for the group of patients receiving NEOCT+Sx+CT/RT risk was reduced to 0.365 (95% CI 0.169-0.787), p=0.010. The corresponding absolute survival benefit was 14% for patients in stages IB2-IIA, 24% for IIB, and 21% for stage IIIB. CONCLUSIONS: Within the limitations of a non-randomized study, our results are in agreement with those obtained from published randomized phase III trials which state that radiation therapy alone is a suboptimal treatment for locally advanced cervical cancer; hence, patients should receive cisplatin-based chemoradiotherapy as a standard treatment.

Adenocarcinoma↗
PubMed2004

Pericardial synovial sarcoma: 14-year survival with multimodality therapy.

We report a case of recurrent primary synovial sarcoma of the pericardium. Reverse transcriptase-polymerase chain reaction analysis for t(X,18) demonstrated the presence of the chimeric transcript SYT/SSX. Because of the rarity of this entity, optimal therapy is unknown. The prognosis of this tumor is very poor in previous reports. In this report, we present a case with five recurrences treated by a combination of surgery, chemotherapy, and radiotherapy. The patient survives now for more than 14 years, the longest reported survival of a primary synovial sarcoma of the pericardium.

Adult↗
PubMed2006

Multimodal assessment of disgust in contamination-related obsessive-compulsive disorder.

The present study utilizes multiple methods to examine the relationship between disgust and contamination-related obsessive-compulsive disorder (OCD) symptoms in an analogue sample. Questionnaire findings revealed that participants with high OCD contamination concerns showed stronger disgust sensitivity than did participants with low OCD contamination symptoms after controlling for negative affect. High OCD participants (N=30) also reported significantly more disgust than did low OCD participants (N=30) when exposed to a disgust-inducing video, whereas no significant between-group differences were detected on other negative emotional dimensions. Results from a series of disgust-specific behavioral avoidance tasks (BATs) revealed that high OCD participants demonstrated both less compliance and less approach behavior. Subsequent analysis also revealed that disgust sensitivity generally mediated avoidance on the BATs among high OCD subjects. High OCD participants also rated the BATs as more fearful and disgusting than did low OCD participants, with disgust generally emerging as the dominant emotional response. The results are consistent with a disgust-based, disease-avoidance approach in understanding contamination-related OCD themes.

Affect↗
PubMed2004

Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach.

We tested the hypothesis that the effects on gene expression of altered DNA methylation by 5-aza-2'-deoxycytidine (5-aza-CdR) and genetic (DNMT knockout) manipulation of DNA are similar, and distinct from Trichostatin A (TSA)-induced chromatin decondensation. Surprisingly, the effects of 5-aza-CdR were more similar to those of TSA than to DNMT1, DNMT3B, or double DNMT somatic cell knockout. Furthermore, the effects of 5-aza-CdR were similar at one and five days exposure, suggesting active demethylation or direct influence of both drugs on the stability of methylation and/or chromatin marks. Agents that induce gene activation through hypomethylation may have unintended consequences, since nearly as many genes were downregulated as upregulated after demethylation. In addition, a 75 kb cluster of metallothionein genes was coordinately regulated.

Algorithms↗
PubMed2006

Managing the symptoms of multiple sclerosis: a multimodal approach.

BACKGROUND: Patients with multiple sclerosis (MS) may experience numerous symptoms, including spasticity, fatigue, cognitive dysfunction, depression, bladder dysfunction, bowel dysfunction, sexual dysfunction, and pain. OBJECTIVE: This article reviews the pharmacologic and nonpharmacologic interventions used to manage the symptoms of MS and discusses how interventions for a particular MS symptom may have an impact on other symptoms. METHODS: The English-language literature was reviewed through November 2005 using MEDLINE and the Cochrane Database of Systematic Reviews, with no restriction on year. The search terms included multiple sclerosis, disease-modifying therapies, adverse events, and combinations of multiple sclerosis with terms such as spasticity, fatigue, depression, mood disorders, pain, bladder dysfunction, bowel dysfunction, sexual dysfunction, cognitive dysfunction, and quality of life. RESULTS: The numerous options for the treatment of MS symptoms have shown varying degrees of efficacy and tolerability. Certain symptoms, if left untreated, may precipitate exacerbation of others. For example, spasticity may lead to pain and bladder and bowel dysfunction, whereas fatigue can compromise cognitive function. Similarly, the adverse effects of treatments for certain symptoms may further compromise other aspects of function. For example, the use of antidepressants may lead to sexual dysfunction, and treatments for spasticity and pain may cause sedation, which can worsen fatigue, cognitive dysfunction, and depressed mood. CONCLUSIONS: MS is associated with numerous symptoms that can be adversely affected by each other and by therapeutic interventions. Careful clinical monitoring and individualization of pharmacologic and non-pharmacologic therapies are recommended to manage the symptoms of MS, with the goals of improving or maintaining function and preserving the patient's quality of life.

Cognition Disorders↗
PubMed2005

Multimodal and three-dimensional imaging of prostate cancer.

Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis.

Humans↗
PubMed2005

Multimodality preoperative imaging of pancreatic insulinomas.

Pancreatic insulinomas are rare tumours of the islet cells of the pancreas, which account for the majority of functional neuroendocrine tumours of the pancreas. There is often a typical history of recurrent hypoglycaemic collapse and dizzy spells. Insulinomas are usually solitary, and the vast majority are intra-pancreatic in location. They are characteristically small with approximately 66% being less than 2cm at presentation. Insulinomas continue to pose a diagnostic challenge to physicians, surgeons and radiologists alike. The role of imaging is to detect and provide precise anatomical localization and staging of tumours prior to surgery. Due to their small size at clinical presentation, they are notoriously difficult to localize radiologically, and specifically designed protocols are necessary to aid detection. In this review, we describe the current "state of the art" imaging protocols that may be used in the preoperative localization of insulinomas.

Aged↗
PubMed2006

Facultative or obligate anaerobic bacteria have the potential for multimodality therapy of solid tumours.

Recent understanding of the unique pathology of solid tumours has shed light on the difficult and disappointing nature of their clinical treatment. All solid tumours undergo angiogenesis that results in biological changes and adaptive metabolisms, i.e. formation of defective vessels, appearance of hypoxic areas, and emergence of an heterogeneous tumour cell population. This micro-milieu provides a haven for anaerobic bacteria. The strictly anaerobic clostridia have several advantages over other facultative anaerobes such as salmonella or lactic acid-producing, Gram-positive, obligate, anaerobic bifidobacteria. Both pathogenic and non-pathogenic clostridia have been demonstrated to specifically colonise and destroy solid tumours. Early trials of non-pathogenic strains in humans had shown plausible safety. Genetic modifications and adaptation of pathogenic and non-pathogenic strains have further created improved features. However, these manipulations rarely generate strains that resulted in complete tumour control alone. Combined modalities of therapies with chemo and radiation therapies, on the other hand, often perform better, including 'cure' of solid tumours in a high percentage of animals. Considering that clostridia have unlimited capacities for genetic improvement, we predict that designer clostridia forecast a promising future for the development of potent strains for tumour destruction, incorporating mechanisms such as immunotherapy to overcome immune suppression and to elicit strong anti-tumour responses.

Angiogenesis Inhibitors↗
PubMed2025

Cardiac hypertrophy at the crossroads: Mechanistic insights and emerging multimodal therapeutic strategies.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, accounting for approximately 17.9 million deaths annually. Among their diverse manifestations, cardiac hypertrophy is a clinically significant condition that predisposes patients to heart failure, arrhythmias, and and sudden cardiac death. Clinically, hypertrophy can be classified into three forms: physiological (adaptive) hypertrophy, which supports cardiac performance and is reversible, pathological hypertrophy most often secondary to hypertension, valvular disease, hemodynamic stress, or sustained neurohumoral activation; and hypertrophic cardiomyopathy (HCM) represents a primary genetic disorder, most often caused by mutations in sarcomeric proteins. These distinct etiologies have important therapeutic implications, as they determine how efficiently pharmacological agents can target underlying mechanisms. Conventional pharmacological treatments are widely used in clinical practice, yet they provide limited reversal of established remodeling. This therapeutic gap has driven the development of innovative modalities such as RNA-based therapeutics, exosome-mediated interventions, stem cell-derived therapies, and genome-editing technologies, which aim to modulate maladaptive signaling and restore myocardial integrity. This review integrates clinical perspectives with mechanistic insights, delineating the drivers of pathological hypertrophy while evaluating both established therapies and emerging strategies that hold promise for precision cardiology and improved patient outcomes.

Humans↗
PubMed2006

Aggressive angiomyxoma: multimodality treatments can avoid mutilating surgery.

AIMS: Aggressive angiomyxoma is a soft-tissue tumour of the pelvi-perineum. The recurrence rate is high, and often extensive resections are performed with considerable morbidity. In search of alternative treatment methods we present our experience in seven patients. METHODS: The medical charts of seven patients treated in the last 20years were reviewed. Follow-up data were obtained. In addition, a literature review from 1994 to 2004 regarding treatment and clinical outcome was performed. RESULTS: All patients were female, and three were pregnant at the time of diagnosis. All patients underwent primary surgical treatment. In five patients the surgical margins were involved; one patient received adjuvant radiotherapy treatment. Three patients experienced a total of four recurrences after 2-10years. These patients were treated with selective embolisation or surgery. At present all patients are disease-free, with follow-up ranging from 2 to 20years after last treatment. CONCLUSION: Radical surgery does not seem to lead to a significant lower recurrence rate of aggressive angiomyxoma when compared to incomplete resection (R1), with or without radiotherapy or arterial embolisation. This casts doubt on the necessity of extensive surgery, especially in cases where an extensive surgical procedure will lead to great morbidity.

Adult↗
PubMed2006

Assessing the predictive validity and efficacy of a multimodal training programme for laparoscopic radical prostatectomy (LRP).

OBJECTIVES: To assess the predictive validity (ability to correlate to real-life environment) and efficacy of a training programme for laparoscopic radical prostatectomy (LRP), based on a structured and progressive pelvitrainer component with hands-on clinical training in the operating room (OR). METHODS: Prospective data on 500 LRP cases were analysed with 80 excluded due to incomplete records. The operation was divided into multiple steps. Times for these steps were compared among 11 surgeons with different laparoscopic expertise (first-, second-, and third-generation surgeons in order of decreasing experience) and correlated to times for specific exercises on the pelvitrainer that simulated particular steps. Perioperative parameters were also evaluated among the three groups. RESULTS: Pelvitrainer times achieved by trainees (third-generation surgeons) did not differ significantly with times for corresponding steps of LRP. There was also no significant difference for total OR time between the second- and third-generation surgeons (205 and 207 min, respectively; p>0.05) although the time for the first-generation surgeons was faster than both (176 min). Short-term quality indicators for first, second, and third generations included transfusion rates (2.3%, 2.4%, and 2.6%, respectively), positive margin rates (20.3%, 21.5%, and 23.0%) and complications, which did not differ significantly among the generations although the first-generation surgeons had the lowest rates. CONCLUSIONS: A carefully designed training programme that incorporates both pelvitrainer and mentor-based operative training is essential for the effective and safe transfer of skills and knowledge required to learn LRP.

Adult↗
PubMed2006

Late effects of enriched environment (EE) plus multimodal early onset stimulation (MEOS) after traumatic brain injury in rats: Ongoing improvement of neuromotor function despite sustained volume of the CNS lesion.

Recently we showed that the combination between MEOS and EE applied to rats for 7-15 days after traumatic brain injury (TBI) was associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction. In a continuation of this work, we tested whether these effects persisted for longer post-operative periods, e.g. 30 days post-injury (dpi). Rats were subjected to lateral fluid percussion (LFP) or to sham injury. After LFP, one third of the animals (injured and sham) was placed under conditions of standard housing (SH), one third was kept in EE-only, and one third received EE+MEOS. Standardized composite neuroscore (NS) for neurological functions and computerized analysis of the vibrissal motor performance were used to assess post-traumatic neuromotor deficits. These were followed by evaluation of the cortical lesion volume (CLV) after immunostaining for neuron-specific enolase, caspase 3 active, and GFAP. Finally, the volume of cortical lesion containing regeneration-associated proteins (CLV-RAP) was determined in sections stained for GAP-43, MAP2, and neuronal class III beta-tubulin. We found (i) no differences in the vibrissal motor performance; (ii) EE+MEOS rats performed significantly better than SH rats in NS; (iii) EE-only and EE+MEOS animals, but not SH rats, showed better recovery at 30 dpi than at 15 dpi; (iv) no differences among all groups in CLV (larger than that at 15 dpi) and CLV-RAP, despite a clear tendency to reduction in the EE-only and EE+MEOS rats. We conclude that EE+MEOS retards, but cannot prevent the increase of lesion volume. This retardation is sufficient for a continuous restoration of neurological functions.

Animals↗