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PubMed2005

Regional analgesia in the critically ill.

OBJECTIVE: The objective of this review is to analyze and describe the use of regional analgesia in the critically ill. DATA SOURCE: A Medline search from 1966 to 2004 using the search terms critically ill, nerve blocks, regional analgesia, and regional anesthesia, as well as a search in the Cochrane library, was performed, and standard international textbooks related to critical care and regional anesthesia were searched for practice recommendations. STUDY SELECTION: Studies, case reports, and review articles relevant to the topic were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted and analyzed in a descriptive fashion. CONCLUSION: Regional analgesia using single-injection regional blocks and continuous neuraxial and peripheral catheters can play a valuable role in a multimodal approach to pain management in the critically ill patient to achieve optimum patient comfort and to reduce physiologic and psychological stress. By avoiding high systemic doses of opioids, several complications like withdrawal syndrome, delirium, mental status changes, and gastrointestinal dysfunction can be reduced or minimized. Because of limited patient cooperation during placement and monitoring of continuous regional analgesia, indications for their use must be carefully chosen based on anatomy, clinical features of pain, coagulation status, and logistic circumstances. High-quality nursing care and well-trained physicians are essential prerequisites to use these techniques safely in the critical care environment.

Analgesia, Epidural↗
PubMed1994

Usefulness of trigeminal somatosensory evoked potentials to detect subclinical trigeminal impairment in multiple sclerosis patients.

Trigeminal somatosensory evoked potentials (TSEPs) by surface electric pulse stimulation were recorded in 30 normal subjects and in 70 multiple sclerosis (MS) patients, 13 of whom presenting clinical trigeminal impairment. We observed significant prolongation of all TSEPs parameters in MS group. TSEPs were abnormal in 45 patients (64.3%). Clinical and neurophysiological data agreed in 36 patients (51%) on 84 sides (60%). TSEPs were able to detect clinically silent lesions 54 times. TSEPs recording proves to be an additional useful test in MS multimodal evoked potential protocols.

Adolescent↗
PubMed2006

Peroxisomal proliferator-activated receptor-gamma agonists induce partial reversion of epithelial-mesenchymal transition in anaplastic thyroid cancer cells.

Anaplastic thyroid cancer (ATC) is an extremely aggressive tumor characterized by marked epithelial mesenchymal transition, which leads, almost invariably, to death. Peroxisomal proliferator-activated receptor (PPAR)-gamma agonists have recently emerged as potential antineoplastic drugs. To establish whether ATC could be a target of PPAR gamma agonists, we first examined PPAR gamma protein expression in a panel of six ATC cell lines and then studied the biologic effects of two PPAR gamma agonists, ciglitazone and rosiglitazone, that belong to the class of thiazolidonediones. PPAR gamma protein was present and functional in all ATC cell lines. Both ciglitazone and rosiglitazone showed complex biological effects in ATC cells, including inhibition of anchorage-dependent and -independent growth and migration, and increased apoptosis rate. Rosiglitazone-induced growth inhibition was associated with cell cycle arrest and changes in cell cycle regulators, such as an increase of cyclin-dependent kinases inhibitors p21(cip1) and p27(kip1), a decrease of cyclin D1, and inactivation of Rb protein. Rosiglitazone-induced apoptosis was associated with a decrease of Bcl-X(L) expression and caspase-3 and -7 activation. Moreover, rosiglitazone antagonized IGF-I biological effects by up-regulating phosphatase and tensin homolog deleted from chromosome 10 with subsequent inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway. Finally, rosiglitazone increased the expression of thyroid-specific differentiation markers. In conclusions, these data suggest that PPAR gamma agonists induce a partial reversion of the epithelial mesenchymal transition in ATC cells by multiple mechanisms. PPAR gamma agonists may, therefore, have a role in the multimodal therapy currently used to slow down ATC growth and dissemination.

Antineoplastic Agents↗
PubMed1999

Extraskeletal Ewing's sarcoma.

BACKGROUND: Ewing's sarcoma usually is identified as a primary malignancy of bone affecting children and young adults. Extraskeletal Ewing's sarcoma is rare, and very few data are available addressing optimal surgical and oncologic treatment modalities. METHODS: The authors chose to review retrospectively 24 patients with extraskeletal Ewing's sarcoma treated at the study institution with modern multimodality therapies. Anatomic location, tumor size, patient age at diagnosis, stage of disease at the time of diagnosis, surgical margins, radiation dose, and the type and dose of chemotherapy were documented for every patient. Follow-up averaged 64 months for surviving patients. RESULTS: The overall 5-year survival rate was 61% and the disease free survival rate was 54%. A multivariate analysis found that younger age at the time of diagnosis was associated with improved 5-year survival and disease free survival (P = 0.008 and P = 0.005, respectively). Patients who underwent wide resection and less-than-wide resection had better overall survival (P = 0.001 and P = 0.015, respectively) and disease free survival (P = 0.002 and P = 0.024) compared with those who underwent no attempt at surgical resection. Patients who underwent a wide resection had an improved overall survival compared with those who underwent a less-than-wide resection (P = 0.045). The size of the lesion (P = 0.277) and the presence of metastatic disease at the time of diagnosis (P = 0.219) were not found to be significant prognostic factors. CONCLUSIONS: Age and surgical treatment were found to be important prognostic variables in the treatment of extraskeletal Ewing's sarcoma. No other variables, such as tumor size, tumor location, stage of disease, or radiation therapy, were found to improve survival. Surgical resection should be considered for all patients with extraskeletal Ewing's sarcoma.

Adolescent↗
PubMed1997

[Identification of major gene and polygene mixed inheritance model and estimation of genetic parameters of a quantitative trait from F2 progeny].

It has been proved by many field experiments and QTL mapping results that among genes affecting some quantitative traits there are some major genes with larger genetic effect and some polygenes with smaller genetic effect. For such traits, the distribution of segregating population demonstrates multimodality, and this is the characteristic of the mixture of more than one distributions. Mixture distribution models have been used extensively as models in a wide variety of practical situations where data can be viewed as arising from two or more populations mixed in certain proportions. Akaike's Information Criterion(AIC) has been used to identify the existence of major genes affecting quantitative traits. Under the existence of major genes, the genetic effects of these genes and their genetic variance were estimated through segregation analysis. The genotype of major gene of F2 individuals of were determined by clustering using Bayesian criterion. With P1, P2, F1 and F2 populations, the likelihood ratio test was used to test the existence of polygenes. In the end, the inheritance of soybean flowering date is analyzed. One major gene was found in F2 population derived from Guludou x Shanghaihongmangzao.

Models, Genetic↗
PubMed1996

Mutant p53 expression: a marker of diminished survival in well-differentiated soft tissue sarcoma.

The aim of this study was to assess the translational value of the quantitative assay of mutant p53 protein expression as both a prognostic indicator and a tool to determine appropriate therapy in a group of relatively innocuous and morphologically similar soft tissue sarcomas (STSs). Using a quantitative ELISA, we analyzed mutant p53 protein expression in 47 well-differentiated (grade I) STSs from patients treated in our Department of Surgical Oncology. Sixteen of 47 tumors expressed up to 42.6 ng mutant p53 protein/mg total protein. After a mean follow-up of 112 months, 63% of the patients with mutant p53+ tumors but only 16% of the patients with mutant p53- tumors had died (P < 0.01). Mutant p53 expression of >/=4.5 ng predicted even greater reduction in survival. These data show that mutant p53 expression identifies biologically aggressive grade I STSs. This molecular marker should have translational value as a tool to select those patients likely to benefit from aggressive multimodal therapy and intense surveillance.

Adolescent↗
PubMed2002

The Mayo Clinic experience with multimodality treatment of locally advanced or recurrent colon cancer.

BACKGROUND: Patients with incompletely resected locally advanced and recurrent colon cancers have a dismal prognosis. Since 1981, 100 colon cancer patients have been treated with combination therapy including surgical resection, chemotherapy, and external plus intraoperative radiotherapy. METHODS: A prospective computerized intraoperative radiation database identified patients for this retrospective review. Data collection included patient demographics, tumor and treatment variables, and morbidity, recurrence, and survival statistics. RESULTS: The mean age was 55.2 years. Follow-up was available for all patients. Fifty-nine patients have died. Median follow-up of survivors was 70.5 months. Twenty-five patients with locally advanced colon cancer had a median survival of 38.2 months and a 5-year survival of 49%. Eleven of these patients are still free of disease. Seventy-three patients treated for recurrent colon carcinoma had a median survival of 33.3 months from the time of recurrence, with a 5-year survival of 24.7%. Twenty-one are alive without evidence of recurrence. The 38 patients with recurrent disease whose disease was completely resected had a 37.4% 5-year survival. CONCLUSIONS: A multimodality approach using en-bloc surgical resection with radiotherapy and chemotherapy affords some patients with locally advanced and recurrent colon cancer a chance for long-term survival.

Adult↗
PubMed2006

The effect of a new multimodal perioperative anesthetic regimen on postoperative pain, side effects, rehabilitation, and length of hospital stay after total joint arthroplasty.

This study evaluated the effect of a new multimodal perioperative anesthetic and pain management strategy for primary total hip (THA) and total knee arthroplasty (TKA). Two cohorts of 50 consecutive THA and 50 TKA patients from before and after initiation of the new protocol were compared. The protocol involved scheduled oral narcotics, cyclooxygenase-2 inhibitors, no intrathecal narcotics, femoral nerve catheters for TKAs, and local anesthetic wound infiltration. Use of patient-controlled analgesia was discouraged. Physical therapy was attempted on the day of surgery. The demographic data, surgical procedure, and implants were similar. There were statistically significant improvements after the protocol regarding rest-pain scores post-operative day (POD) 1 and 2, total narcotic consumption, distance walked POD 1 and 2, and length of stay. There were no significant differences in complications. Implementation of this new multimodal perioperative protocol combined with early mobilization for TKA and THA patients has shortened length of stay, improved pain control, and accomplished therapy goals sooner with less narcotic consumption.

Anesthesia, Epidural↗
PubMed1999

Automated registration of multimodal brain image sets using computer vision methods.

We present a new method of registering three dimensional image volumes of the brain of a given patient acquired at different times or with different imaging modalities, or both. Registration is an essential requirement for fusing the data from the two image sets so as to either increase the available information by exploiting complementary imaging modalities, or to measure small changes over time for prognostication, disease assessment, etc. The new technique exploits an external, removable, remountable reference frame which is attached to the head. Computer vision techniques are used to determine the positions of fiducial marks in every image. The transformation required to map each image of one image volume onto the other image volume is developed using the theory of quaternions. The results indicate that the new technique is robust and practical in a clinical setting.

Algorithms↗
PubMed2001

Comparative study of the effects of auditory, visual and multimodality displays on drivers' performance in advanced traveller information systems.

A simulator study was conducted to compare 16 younger (mean age 22 years) and 16 older (mean age 68 years) drivers' ratings of workload (time, visual, psychological stress) and performance of navigation and button-pushing (identification of vehicle or road hazards) tasks under both high- and low-load driving conditions when simple or complex advanced traveller information (ATI) was presented visually only, aurally only or by multimodality (visual and auditory) display. For all participants, both the auditory and multimodality displays produced better performance in terms of response times, total number of correct turns and subjective workload ratings than those of using the visual-only display. Participants using the multimodality display also made the fewest errors related to push-button and navigation tasks, and controlled their vehicles properly. The visual display led to less safe driving, apparently because it imposed higher demands on the drivers' attention. An age effect was found in the present study, with younger drivers performing better and reporting less stress than older drivers. Notably, however, use of the multimodality display significantly improved the older drivers' performance in the button-pushing task.

Adult↗
PubMedDate not supplied

[Clinical, multimodal electrophysiological study of a family with progressive cerebellar ataxia and late deafness and an autosomal recessive inheritance].

We described the clinical, electrophysiological (electromyography, sensory and motor nerve conduction study, somatosensory evoked potentials, brainstem auditory evoked potentials, visual evoked potentials) and neuroradiological (brain magnetic resonance) data in 3 siblings (2 males and 1 female, age range: 54-48 years) affected by autosomal recessive late onset cerebellar ataxia. The 3 patients showed at the electrophysiological examination: mild peripheral neuropathy, involvement of somatosensory pathways both on central and peripheral side. A mild cerebellar atrophy, most evident in the female more severely disabled, was found by magnetic resonance.

Atrophy↗
PubMed2001

Functional recovery and regeneration of descending tracts in rats after spinal cord transection in infancy.

STUDY DESIGN: The functional recovery of rats that underwent spinal cord transection in infancy was evaluated by multimodal examination (functional tests, electrophysiologic evaluation, tract-tracing) to determine the basis for the recovery. OBJECTIVES: To determine whether the hind limb function in rats that underwent spinal cord transection in infancy is regained completely, which descending tracts regenerate after the transection, and whether the functional recovery is correlated with axonal reconnection. SUMMARY OF BACKGROUND DATA: It is widely accepted that a newborn rat recovers its hind limb function after spinal cord transection even without any specific treatments. This functional recovery might be attributed to possible regeneration of some descending pathways, although there is a counterargument that well-trained spinal cord reflexes may bring about functional compensation. METHODS: The thoracic spinal cord of infant rats was completely transected at Th10 when they were 2 weeks of age. Multimodal functional tests and electrophysiologic studies were performed 5 weeks later. Some recovered rats (i.e., those able to walk after the transection) underwent spinal cord retransection, with subsequent reevaluation of locomotion and muscle-evoked potentials. At 6 weeks after the initial transection, tract-tracing studies were performed in some animals. RESULTS: A motor performance score detected the functional differences between the control and the recovered rats. Muscle-evoked potentials of hind limbs after electrical stimulation to the brain were recorded in some of the recovered rats, but never in the unrecovered rats. Moreover, the muscle-evoked potentials of the recovered rats disappeared after spinal cord retransection that resulted in loss of voluntary movement. Morphologic studies in two rats provided evidence that reconnection of rubrospinal, vestibulospinal, and reticulospinal tracts had occurred, whereas corticospinal regeneration was not detected. CONCLUSIONS: It can be concluded that the hind limb function of rats that underwent spinal cord transection in infancy was partially regained; that axonal regeneration of the rubrospinal, vestibulospinal, or reticulospinal tracts was demonstrated, whereas the reconnection of the corticospinal tract was not observed; and that the axonal regeneration of these tracts is involved in the functional recovery.

Animals↗
PubMed1997

A three-dimensional multimodality brain map of the nemestrina monkey.

A three-dimensional multimodality computerized map of the nemestrina monkey brain was created with serial sectioning and digital imaging techniques. An adult female Macaca nemestrina (pigtail macaque) weighing 7.2 kg was used in constructing this atlas. CT, PET, and MRI were performed on the monkey before the specimen's head was frozen and cryoplaned. Closely spaced (50 microns) images of the specimen blockface were then digitally acquired and modified to produce whole head and brain-only 3D image sets. The resulting data sets were organized into a digital volume and repositioned into a stereotaxic coordinate system defined by Horsley and Clark in 1908 [7]. Orthogonal images were obtained by digitally resampling the volume in order to produce a full set of coronal, sagittal, and horizontal images. Stereotaxic reference grids were applied to each image indicating the A/P, M/L, or Ho position within the digital volume. Specific anatomic structures were outlined from the cryosection data set and 3D surface models reconstructed. Structural labels indicating nuclei, tracts, and other neuroanatomical features were incorporated into coronally sliced cryosection images spaced at 500 microns. The CT, PET, and MRI data sets were reconstructed into a digital volume and coregistered to the cryosection volume. All images constructed from this 3D map are available for public access via the internet using an anonymous file transfer protocol (FTP) and the World Wide Web (http:@www.loni.ucla.edu). The foremost advantage of this digital map is an integrated multimodality three-dimensional representation of the Macaca nemestrina brain, which is not possible with traditional atlases.

Animals↗
PubMed2004

Multimodal treatment for ADHD among youths in three Medicaid subgroups: disabled, foster care, and low income.

OBJECTIVE: This study compared the use of treatments for attention-deficit hyperactivity disorder (ADHD) among three distinct subpopulations of Medicaid-insured youths who have very different mental health needs and patterns of service use: those with federally documented disability, those in foster care, and those in families with low income. METHODS: This one-year, cross-sectional study of community mental health services used administrative data. Individuals who were younger than 20 years, who were continuously enrolled in one Mid-Atlantic state Medicaid program, and who had two or more medical encounters associated with an ADHD diagnosis in 1998 were identified (N=1,296). Measures of the use of mental health services were the number of different classes of psychopharmacologic medications, the psychopharmacologic regimen, and the combined use of pharmacotherapy and psychotherapy treatments (multimodal treatment). RESULTS: Use of multiple psychopharmacologic agents was greater in the disabled and foster care groups compared with the low-income group. Significantly fewer mental health provider visits, but greater use of stimulant treatment only, were observed in the low-income group compared with the other groups. Youths in the disabled group were significantly more likely than youths in the low-income group, but not more likely than youths in the foster care group, to receive multimodal treatments. Children in foster care were significantly more likely than those in the other groups to use a substance abuse service. CONCLUSIONS: Among a cohort of Medicaid-enrolled youths with ADHD, co-existing psychiatric disorders and complex psychopharmacologic treatments were more common in the disabled and foster care groups than in the low-income group. Youths with disabilities were significantly more likely than youths in the low-income group to receive multimodal treatment.

Adolescent↗
PubMed2007

Impact of interferon-alpha in combined chemoradioimmunotherapy for pancreatic adenocarcinoma (CapRI): first data from the immunomonitoring.

Data from a phase II trial combining chemoradiotherapy with IFN-alpha (CapRI scheme) for adjuvant treatment of pancreatic carcinoma are very encouraging. Therefore, a phase III trial comparing chemotherapy with the chemoradiotherapy with IFN-alpha scheme has been initiated in August 2004. Translational research with a focus on immunomodulation is performed in parallel to the study. Blood and serum samples are taken at various time points. Patients in arm A (chemoradioimmunotherapy) receive a single low-dose-Interferon injection before therapy to investigate the direct effect of IFN-alpha. So far samples from 44 patients have been investigated for surface molecule expression, cytokine levels, natural killer cell cytotoxicity, and antigen-specific Granzyme B release. Patients in arm A showed 1 day after IFN-alpha injection a significant increase in spontaneous cytotoxicity; this effect was fading after repeated injections. Furthermore, cells releasing Granzyme B after stimulation with CA 19.9 and MUC-1 protein increased under therapy. Five days after the first IFN-alpha injection, IL-12 and TNF-alpha serum levels peak. We observed significant increases of monocytes, peripheral dendritic cells, CD40 cells, central and effector memory T cells, and CD8 cells, CD4 cells decreased during therapy. All these effects were only observed in arm A patients and none of them in arm B patients. In conclusion, in a translational research project accompanying a challenging multimodality treatment trial including IFN-alpha, we observed an immediate activation of antigen-presenting cells and natural killer cells followed later on by antigen-specific activation. It will be most interesting if the immunologic data will show a correlation with the clinical course of the patients.

Adenocarcinoma↗
PubMed2005

Prenatal hypoxia impairs memory function but does not result in overt structural alterations in the postnatal chick brain.

We showed previously that hypoxia in ovo impairs memory consolidation in the chick tested 2 days after hatching. Our present aim was to investigate whether we could detect any morphological effects of the same prenatal hypoxia. Hypoxia was induced by half-wrapping the egg with an impermeable membrane from either days 10-18 (W10-18 chicks) or days 14-18 (W14-18 chicks) of incubation (hatching approximately 21 days). Measurement of blood gases showed that reducing the surface area of the egg for gas exchange resulted in reduced pO2 and increased pCO2 2 days after wrapping. Although this hypoxia was sufficient to impair cognitive processing in the postnatal chick, our data suggest that it did not produce overt structural alterations or changes in the number of neurons, glutamine synthetase-immunoreactive cells or immunoreactivity to synaptophysin in the presynaptic vesicles in the multimodal integration (cortical) area compared to controls. Hence, we found no differences in the astrocyte to neuron ratio, synaptic density and/or vesicle number. Analysis of the ontogeny of astrocytes during the prenatal period of hypoxia showed them to be present at embryonic day 12, but not at the earlier ages examined. Although we found cognitive deficits in chicks from embryos made hypoxic during incubation, our regimen of prenatal hypoxia did not alter any of the parameters measured in the brains. This does not preclude the possibility that changes have occurred at the cellular or molecular levels or in specific neurotransmitter systems.

Animals↗
PubMed2003

Positive cooperativity induces multimodal site and thermodynamic affinity distributions in multivalent proteins.

The characterization of the stoichiometric and site-affinity distributions for the reaction of hemoglobin with O(2) and CO is presented as an example of a multivalent receptor system which exhibits positive site-site interactions. The distributions of stoichiometric constants, T(i)(K(i))'s, are obtained assuming that the distribution of site constants, N(k), is known. The importance of these distributions is that they can be directly related to quantities measured experimentally and that they represent affinity distributions for each ligation step. In hemoglobin, positive site-site interactions generate both stoichiometric and site-affinity distributions with complex and previously unrecognized multimodal patterns that are very different from the theoretical distributions obtained in the absence of interactions. These distributions are related to the generation of heterogeneity during the ligand binding process. Experimental binding data show that these complex distributions can be related to the physiological functions of uptake, transport, and release of gaseous ligands by hemoglobin.

Binding Sites↗
PubMed2005

Remarkable impact of intermode couplings on multimode vibronic dynamics: the photoelectron spectrum of CH3F.

Electronic and nuclear motions on intersecting potential energy surfaces are often intricately mixed and the spectrum can become very complex. Here we choose the strongly coupled Jahn-Teller system CH3F+ as a prototype example, and establish the importance of intermode coupling terms on multimode vibronic dynamics. The theoretical approach consists of a full second-order diabatic vibronic Hamiltonian, constructed from high-quality electronic structure calculations. Our results compare amazingly well with the experimental data. This highlights the success of the present theoretical approach in explaining the complex structure of vibronic spectra, ubiquitous in molecular systems.

Journal Article↗