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PubMed2006

Is radical prostatectomy feasible in all cases of locally advanced non-bone metastatic prostate cancer? Results of a single-institution study.

OBJECTIVES: Previous prospective studies of the surgical treatment of locally advanced prostate cancer have enrolled patients selected on the basis of a limited T3 disease extension. The aim of the present study was to assess the feasibility and the oncologic outcome of radical prostatectomy administered to a consecutive unselected series of advanced, non-bone metastatic prostate cancers. METHODS: Between March 1998 and February 2003 radical prostatectomy was offered at our institution to any patient diagnosed with prostate cancer with no sign of extranodal metastatic disease. Data on morbidity and survival for 51 clinically advanced cases (any T>/=3, N0-N1, or any N1 or M1a disease according to the TNM 2002 classification system) operated on by a single expert surgeon were compared with a series of 152 radical prostatectomies performed during the same period by the same operator for clinically organ-confined disease. Adjuvant treatment was administered according to current guidelines. RESULTS: The two groups did not differ significantly in surgical morbidity except for blood transfusion, operative time, and lymphoceles, which showed a higher rate in patients with advanced disease. The Kaplan-Meier estimate of overall survival and prostate cancer-specific survival at 7 yr were 76.69% and 90.2% in the advanced disease group and 88.4% and 99.3% in the organ-confined disease group, respectively. CONCLUSIONS: Even in the scenario of extensive surgical indications up to M1a disease, radical prostatectomy proved to be technically feasible and to have an acceptable morbidity rate compared with organ-confined disease. Our initial survival data strengthen the role for surgery as an essential part in the multimodal approach to treating advanced prostate cancer.

Aged↗
PubMed2002

Modulation of the atypical multidrug-resistant phenotype by a hammerhead ribozyme directed against the ABC transporter BCRP/MXR/ABCG2.

The phenomenon of multidrug resistance (MDR) in human cancers is one of the major causes of failure of chemotherapy. A recently identified new member of the superfamily of ATP-binding cassette transporters, breast cancer resistance protein (BCRP), was demonstrated to confer an atypical multidrug-resistant phenotype to tumor cells. To overcome the BCRP-mediated drug resistance, a specific anti-BCRP hammerhead ribozyme was introduced into the human gastric carcinoma cell line, EPG85-257RNOV, exhibiting an atypical MDR phenotype. By this approach, the expression levels of the targeted BCRP-encoding mRNA and the BCRP transport protein were decreased to the low constitutive expression level that was observed in highly drug-sensitive parental gastric carcinoma cells. In addition, in the anti-BCRP ribozyme-treated cells, the cellular drug accumulation was dramatically increased to the level measured in drug-sensitive cells. These effects were accompanied by an extensive reversal of the drug-resistant phenotype of more than 80%. Because additional mechanisms contribute to the multimodal-mediated MDR phenotype exhibited by this gastric carcinoma cell line, the data suggest that the BCRP-mediated contingent to the drug resistance was overcome nearly completely. Moreover, the data indicate that ribozyme-based gene therapy may be clinically applicable in preventing and reversing BCRP-mediated atypical MDR.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1992

Atomic force microscopy of reovirus dsRNA: a routine technique for length measurements.

Atomic force microscopy (AFM) was used to image reovirus double stranded RNA (dsRNA) deposited from diluted buffer solution onto a chemically treated mica surface. This procedure allows AFM images of dsRNA molecules to be obtained with a quality close to that obtained with conventional electron microscopy. The length of the molecules were measured directly on a computer display using the digitally acquired images. The lengths of the molecules varied between 0.2 and 1.8 microns. Statistical analysis showed a multimodal distribution with clear maxima at 0.4, 0.65 and 1.05 microns. These data are in a good agreement with those obtained by electron microscopy and gel electrophoresis.

Microscopy, Scanning Tunneling↗
PubMed1997

Prediction of success from a multidisciplinary treatment program for chronic low back pain.

STUDY DESIGN: The study included 90 disabled patients with chronic low back pain recruited from a pain clinic who were admitted to an 8-week program of functional restoration and behavioral support. Initial evaluations included a medical examination, rating of the physical impairment, a personal interview, a visual analogue scale to record pain intensity, an assessment of limitations for daily activities, a pain disability index, a depression and psychovegetative scale, and a scale to evaluate general living standards. The physical assessment included different flexibility measurements, measurement of power and endurance through standardized exercises, and measurements of isokinetic trunk and lifting strength and general endurance. The measurements were repeated at the end of the 8-week program and thereafter an intervals of 6 and 12 months. Final analyses were carried out on 82 patients. OBJECTIVES: To determine whether objective or subjective signs most influence the outcome of rehabilitation. SUMMARY OF BACKGROUND DATA: In recent years, several studies have shown that active and intensive multimodal treatment of chronic low back pain is successful. Until now there has been lack of information about which patients will respond to the therapy and what is the most effective part of treatment. METHODS: Prognostic factors (return to work, pain intensity, self-assessment of treatment success by patients) were tested by studying variance and regression analyses for their ability to predict treatment outcome. RESULTS: Certain factors were identified that had a significant impact on determining the probability of a patient's return to work and the reduction of pain intensity. These factors included self-evaluation for predicting a return to work, the length of absence from work, application for pension, and a decrease is disability after treatment. Overall satisfaction with treatment was best determined by the number of medical consultations before treatment, the extent of disability, previous measures taken for coping with the disease, and reduction of disability during treatment. Medical background, medical diagnosis, and physical impairment had no predictive value. Physical variables (i.e., mobility, strength, endurance, and physical performance) also demonstrated only limited predictive value. CONCLUSION: This study has demonstrated that the most important variable in determining a successful treatment of chronic low back pain is the reduction of subjective feelings of disability in patients.

Adult↗
PubMed2002

Local frequency representations for robust multimodal image registration.

Automatic registration of multimodal images involves algorithmically estimating the coordinate transformation required to align the data sets. Most existing methods in the literature are unable to cope with registration of image pairs with large nonoverlapping field of view (FOV). We propose a robust algorithm, based on matching dominant local frequency image representations, which can cope with image pairs with large nonoverlapping FOV. The local frequency representation naturally allows for processing the data at different scales/resolutions, a very desirable property from a computational efficiency view point. Our algorithm involves minimizing-over all rigid/affine transformations--the integral of the squared error (ISE or L2 E) between a Gaussian model of the residual and its true density function. The residual here refers to the difference between the local frequency representations of the transformed (by an unknown transformation) source and target data. We present implementation results for image data sets, which are misaligned magnetic resonance (MR) brain scans obtained using different image acquisition protocols as well as misaligned MR-computed tomography scans. We experimently show that our L2E-based scheme yields better accuracy over the normalized mutual information.

Brain↗
PubMedDate not supplied

Research-oriented image registry for multimodal image integration.

To provide multimodal biomedical images automatically, we constructed the research-oriented image registry, Data Delivery System (DDS). DDS was constructed on the campus local area network. Machines which generate images (imagers: DSA, ultrasound, PET, MRI, SPECT and CT) were connected to the campus LAN. Once a patient is registered, all his images are automatically picked up by DDS as they are generated, transferred through the gateway server to the intermediate server, and copied into the directory of the user who registered the patient. DDS informs the user through e-mail that new data have been generated and transferred. Data format is automatically converted into one which is chosen by the user. Data inactive for a certain period in the intermediate server are automatically achieved into the final and permanent data server based on compact disk. As a soft link is automatically generated through this step, a user has access to all (old or new) image data of the patient of his interest. As DDS runs with minimal maintenance, cost and time for data transfer are significantly saved. By making the complex process of data transfer and conversion invisible, DDS has made it easy for naive-to-computer researchers to concentrate on their biomedical interest.

Computer Communication Networks↗
PubMed1981

Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure.

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEP's), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEP's represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

Adult↗
PubMed1991

Multimodality evoked potentials and neurological phenomenology in patients with multiple sclerosis and potentially related conditions.

A comparative study of evoked potential recordings and neurological phenomenology was performed in 151 patients. The material included 95 subjects with MS, myelopathy of unverifiable etiology or optic neuritis. Multimodality evoked potentials (VEP, BAEP, median and tibial nerve SEP) and clinical data were evaluated independently. The highest rates (86-98%) of evoked potential abnormalities were found in patients with MS (clinically definite or probable) and myelopathies. More than one pathological evoked potential modality occurred in 47-69% of these subjects. Tibial nerve SEP yielded the highest frequency of abnormalities. The occurrences of silent lesions and missed lesions (i.e. normal evoked potentials in spite of clinical manifestations) were investigated for the various evoked potential modalities. Silent lesions were detected in 50-68% of the MS and myelopathy patients; SEP and VEP exhibited similar abnormality rates for clinically unaffected pathways. Missed lesions most often occurred for BAEPs but were not uncommon for the other modalities. Further evaluation of the SEP data revealed significant differences of amplitudes between patients with missed lesion and controls.

Adult↗
PubMed1998

Apoptosis in esophageal cancer following induction chemoradiotherapy.

BACKGROUND: The poor survival of patients with esophageal cancer following esophagectomy has led to intense investigation into combined modality therapy. Based on results from clinical trials examining chemoradiotherapy alone without surgery, resection has come under increased scrutiny and its necessity as a component of a multimodal approach has been questioned. In this study, we examined whether residual tumor cells in esophagectomy specimens following induction chemoradiotherapy are viable and, therefore, provide putative evidence for the appropriateness of esophagectomy. MATERIALS AND METHODS: Between August 1991 and January 1995, 46 patients were entered into an induction chemoradiotherapy trial consisting of 5-fluorouracil, cisplatin, alpha-interferon, and concurrent external beam radiotherapy followed by esophagectomy. Response was determined histologically and apoptosis assessed with a terminal deoxytransferase assay system. p53 status was determined by immunohistochemistry and mutational analysis. RESULTS: Thirty-eight patients underwent esophagectomy, 33 of whom had either a complete (n = 10) or partial (n = 23) response. None of the 28 patients with residual tumor in the resected specimen had 100% apoptotic cells and the vast majority of specimens had less than a 10% apoptotic rate. The percentage of apoptotic cells did correlate with tumor differentiation but not with histologic type nor presence of p53 mutations. CONCLUSIONS: These data suggest that resection following upfront chemoradiotherapy is a necessary component of a multimodality approach to esophageal cancer and will ultimately provide superior local-regional control to a nonsurgical approach.

Adult↗
PubMed1984

Monitoring clinical research. A report from the Childrens Cancer Study Group.

This report describes an evaluative approach in assessing study quality in clinical trials. The size of the data set required is defined using decision analysis methods. Assuming entry of eligible patients, the minimum data set required in determining study quality includes: the treatment agent, the protocol stipulated treatment time, and the actual time of administration. While toxicity, complication and response data are primary for the resolution of the scientific issues, they are secondary for study performance questions. Separation of study performance and scientific questions simplifies the design and execution of complex, multimodal, multidisciplinary clinical trials. Application of separate criteria for study performance and scientific questions enhances understanding of protocol requirements by data managers, physicians, and nurses. Once study performance issues are resolved, the scientific issues addressed by the protocol can be considered in detail. The usual practice of focusing on science and study performance simultaneously precludes efficient consideration of either data set. The distinction between analyses of study performance and of scientific questions is illustrated using data from Childrens Cancer Study Group protocol CCG-551. This study is a controlled trial of therapies for non-Hodgkin's lymphoma. The protocol provides an example of modern diagnostic and therapeutic management complexities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Retrospective fusion of radiographic and MR data for localization of subdural electrodes.

Prior to epilepsy surgery, subdural electrodes are often implanted and monitored for a few days to identify the focus of abnormal electrical activity. During the implantation and subsequent brain resection, there may be uncertainty about the exact location of the electrodes with respect to features of brain anatomy such as specific gyral convolutions or lesions. In experiments with a phantom and patients, implanted electrodes were imaged with multiplanar skull radiographs (or CT scans). After retrospective registration with preimplantation MR data, the electrodes were mapped from these studies onto an MR-derived three-dimensional brain model. The resulting multimodality displays showed the relationship of the electrodes to brain anatomy. In one patient the position of each electrode with respect to a metabolic lesion was also displayed by mapping preimplantation PET data onto the same brain model. This new display of electrode positions may strengthen the interpretation of subdural electrical recordings and thereby reduce uncertainty in planning the resection of epileptic tissue.

Adult↗
PubMed2003

Pain disaggregation theory--statistical nonsense or a pointer to a paradigm for quantum nociception?

BACKGROUND: The various patterns of patients' experience of treated acute post-thoracotomy pain exemplify the phenomenon of disaggregation. The intent in this study was to define a theory of disaggregation with a hard-wired neuroanatomical model of thoracotomy pain. METHODS: In order to distinguish the disaggregated nociception conducted along one of three possible pathways, the vagus, the phrenic and, in this study, the intercostal nerves, data from 143 patients undergoing thoracic surgery, and that from two previously conducted studies of multimodal analgesic regimens, were reviewed. The values of one subjective outcome measure (verbal rating score) at different stress levels-at rest, on raising the arm, and on coughing (dynamic pain scores)-were used to construct individuals' charts (pain profiles) of the progress of pain relief over time. These were batched, and analysed using statistics of summary measures. RESULTS: This was a crude exercise in the handling of redundant data, but there is a suggestion that it is possible to distinguish a disaggregated route by an effect of a treatment on a mass of nociception. CONCLUSIONS: This information could underpin a paradigm of quantum nociception, and has potential to quantify aspects of analgesia practice and current and future neurophysiological theories of pain. Prospective studies are warranted.

Analgesia↗
PubMed2003

Multimodal distribution versus logarithmic transformation of thyroid volumes in adolescents: detection of subgroup with subclinical thyroid disorders and its impact on the assessment of the upper limit of normal thyroid volumes.

Our objective was to evaluate whether there is a multimodal distribution of thyroid volume (ThV) in iodine-replete adolescents and to examine the relation between excessive ThV and the presence of thyroid hypoechogenicity (HE), serum thyroperoxidase antibodies (anti-TPO) and TSH levels >4.5 mU/l. ThV was measured by ultrasound in adolescents aged 13 yr (N = 1083) and 17 yr (N = 1089) from 22 schools in 6 districts of eastern Slovakia and expressed as ml and ml/m2 body surface area. For each age group the multimodal distribution of ThV values was tested by computing their frequency at intervals of 0.5 m/m2 and plotting the cumulative frequency on a probability scale in which each segment with normal distribution should give a straight line. In all examined subjects the HE was evaluated by ultrasound; in 924 (42.5%) of those anti-TPO was estimated by radioimmunoassay and TSH by immuno-electrochemiluminiscent assay. The medians of urinary iodine found in 55-164 spot urine samples from each of 6 districts (total number = 1003) were 126-142 microg/l, indicating an iodine-replete status. There was a trimodal distribution of ThV in each group, 80-85% in the lowest, 10-15% in the middle, and 5-7% in the upper segments. In the 10th ThV decile of the 17-yr group the frequency of HE (33/109 = 30.3%), anti-TPO (13/62 = 21.0%) and TSH (6/62 = 9.7%) was significantly higher than that in the 1st-9th decile (71/980 = 7.2%, P<0.001; 23/482 = 4.8%, P<0.001 and 5/482 = 1.0%, P<0.001, resp.). Similar differences were found in the 13-yr group (21/109 = 19.2% vs. 58/974 = 5.9%, P<0.001 for HE, 5/60 = 8.3% vs. 3/320 = 0.9%, P<0.001 for anti-TPO and 2/64 = 3.1% vs. 4/317 = 1.3% (not significant) for TSH >4.5 mU/l. Thus in the 10% of subjects with the highest ThV, the frequency of HE and anti-TPO was 4-5 times higher than in the remaining 90%. Our data indicate that an epidemiological evaluation of a large population of adolescents can detect a group with early signs of thyroid dysfunction (e.g. excessive ThV, increased frequency of HE, anti-TPO and TSH >4.5% mU/l), although such dysfunction may not be clinically apparent. This contrasts with numerous earlier reports which used a logarithmic transformation of the data in similar ThV sets, thus making the data appear homogeneous (unimodal) and with a normal distribution and obscuring the true multimodal distribution. This further prevents recognition of subjects with evidence of disordered thyroid status which thus become falsely included into a normal range.

Adolescent↗
PubMed2001

Multimodality neuroimaging: research and clinical applications.

This manuscript reviews the current stance and the pertinent problems of transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) as brain mapping methodologies. The missing structure-function relation limits the use of TMS, whereas the uncertainty about the functional significance of activated cortical regions might render interpretation of fMRI studies difficult. Advances in image processing, however, allowed for 3- dimensional real-time visual guidance of TMS and integration with fMRI data. We describe the method used to coregister TMS and fMRI and present examples where a multimodality neuroimaging approach might add to our understanding of normal and pathological brain function.

Brain Mapping↗
PubMed2004

Multimodality management of 26 skull-base chordomas with 4-year mean follow-up: experience at a single institution.

OBJECTIVE: To analyze a series of patients with pathologically confirmed skull-base chordoma, and to develop an algorithm for the management of this challenging disease based on the data, our experience, and the current literature. MATERIAL AND METHODS: Between the years 1986 and 2001, 26 chordoma patients received multimodality treatment with various combinations of conventional surgery, skull-base surgical techniques, and gamma-knife surgery at the Marmara University Faculty of Medicine. A total of 57 procedures (43 tumor excision surgeries, 7 gamma-knife procedures, and 7 other operations to treat complications) were performed. The mean follow-up period was 4 years (48.5 months). Karnofsky scoring was used to follow the patients' clinical conditions, and magnetic resonance image analysis was used to measure tumor volume over time. RESULTS: Seven patients died during follow-up. Two of the deaths were due to surgical complications, four resulted from clinical deterioration related to tumor recurrence, and one was unrelated to neoplasia. The rate of tumor recurrence after the first surgical treatment was 58%. Residual tumor volume was lower in the cases in whom skull-base approaches were used as first-line management. The 19 survivors showed little change in clinical status from initial diagnosis to the most recent follow-up check. The mean follow-up time after gamma-knife treatment was 23.3 months. During this period, mean tumor volume increased 28% above the mean volume at the time of gamma-knife surgery. The mean Karnofsky score decreased by 6% during the same time frame. CONCLUSIONS: The most effective first-line treatment for chordoma patients is surgery. The findings for residual tumor volume indicated that skull-base approaches are the best surgical option, and the complication rates for these techniques are acceptable. However, it is rare that surgery ever biologically eradicates this disease, and the data showed that these chordomas almost always progress if the tumor volume at the time of diagnosis exceeds 20 cm(3). Based on our experience and the biological character of the disease, we now advocate radiosurgical treatment (gamma-knife in our case) immediately after the first-line skull-base surgery when the tumor residual volume is <30 cm(3).

Adolescent↗
PubMed1983

Periodic, multimodal distribution of granule volumes in mast cells.

The areas of 2327 mast cell granules in transmission electron micrographs of sections of peritoneal mast cells from adult rats were measured by digitized planimetry. A histogram constructed using equivalent volumes calculated from the measured areas assuming approximation of the granules to spheres showed a periodic multimodal distribution in which the modes fell at volumes that were successively larger integral multiples of the volume at the first mode. Application of a moving-bin technique to the data confirmed the presence of the modes. We propose a mechanism of fusion of unit sized granules to account for the multimodal distribution. The presence of pear- and dumbbell-shaped granules in mast cells is consistent with this mechanism.

Animals↗
PubMed1997

Magnetic resonance: a multimodal approach to the brain?

Magnetic resonance of the brain offers the unique possibility of acquisition of morphological data in high resolution quality, analysis of metabolic disturbances, and the assessment of brain function. Basic principle is the BOLD effect, using the difference of the magnetic moments of oxy- and deoxyhemoglobin as intrinsic mechanism of contrast. Still the optimum techniques for functional imaging are not established: echo planar imaging requires a very costly hardware, whereas gradient echo imaging is feasible on clinical routine MR scanners. Although many experimental studies have been published on visual, motor, and auditory paradigms, clinical applications have not been established up to now. Analysis of epileptogenic foci combining high resolution imaging and functional information seems very promising as well as preoperative determination of critical areas in neurosurgery.

Brain↗
PubMed1999

Mother and teacher reports of ADHD symptoms: DSM-IV Questionnaire data.

OBJECTIVE: Diagnosis of attention-deficit/hyperactivity disorder (ADHD) is thought to be best accomplished by a multimodal approach. In many research and clinical settings, such extensive procedures may not be feasible. A screening instrument that could identify children meeting necessary (but not sufficient) criteria would permit selection of subgroups for more resource-intensive diagnostic procedures. METHOD: The Diagnostic Rating Scale (DRS) was completed by the mothers and teachers of 124 children referred to hospital-based clinics and 225 nonreferred children. The authors performed principal components analysis (PCA) on the questionnaire, compared the scores obtained by children from the 2 samples, and examined age and gender effects. Diagnoses derived from the DRS were not validated against structured diagnostic interviews. RESULTS: PCAs replicated the DSM-IV symptom combinations. Children from the referred sample exhibited more symptoms (p < .001) than children from the community sample. Boys were overrepresented among the children who received DRS-derived ADHD diagnoses. Girls were more likely (92%) to receive a diagnosis of ADHD, predominantly inattentive subtype, than other ADHD diagnoses. CONCLUSIONS: The results of this study provide preliminary support for the validity of the parent and teacher DRS as time- and resource-efficient screening instruments for examining symptoms associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗