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Functional cranial neuronavigation. Direct integration of fMRI and PET data.

OBJECTIVE: We report our first experiences with the direct integration of fMRI data into cranial neuronavigation. METHOD: For navigation we used the MKM system and thin-sliced T1 contrast enhanced images. As a first step 21 patients had fMRI for localization of the precentral gyrus, 2 patients for Broca area detection. By anatomical correlation, these functional data were indirectly compared to the intraoperative findings using cortical SSEP (n=20) or cortical stimulation (n=3). Encouraged by these preliminary results, we started the direct integration of fMRI into neuronavigation in June 1999, followed by PET in January 2000, enabling us to compare functional images with intraoperative findings directly. fMRI and PET data were integrated by landmark matching referring on skin fiducials. Meanwhile, fMRI data of 8 patients (6 motorcortex, 2 Broca) and PET images of 1 patient were directly integrated into neuronavigation. Six out of 8 patients had additional cortical monitoring, 2/8 were exclusively operated on by functional neuronavigation. RESULTS: Using indirect comparison between fMRI and intraoperative findings we observed a good correlation in every case for the motorcortex, but only in 1/2 for the speech area. In all 6 direct integrated fMRI cases, these findings corresponded well to the conventional ones. Both patients with sole functional navigation did not have any postoperative neurological deficit. The inaccuracy of the fMRI ifT1 matching was 2. 7 mm (sigma=0.9 mm) and 1.3 mm (sigma=0.4 mm) of the subsequent referenciation of the navigation. The tumor delinement shown by 11C-methionine PET could be proven by intraoperative biopsy outside its indicated tumor margin. The inaccuracy of the PET matching was 0. 8 mm. CONCLUSION: Functional neuronavigation enables to visualize and preserve relevant brain areas. Other functional areas like short-term memory, which solely can be detected by fMRI might also be monitored in the future. The integration of PET data expect to gain a better differentiation of tumor and edema.

Adult↗

Psychoimmuno-neuroendocrinology: An integrative approach to modern philosophy in medicine and psychology.

The immune system is now seen to be closely integrated with other physiological circuits, such as the central nervous system (CNS) and the neuroendocrine system. There is also an increasing amount of evidence that this integrated circuit is bidirectional and both systems exert a reciprocal effect on each other. We have always stressed the interdisciplinary nature of the science where disciplines and sciences such as medicine, biochemistry, genetics, psychology, human ethology, etc. meet and undergo a process of "cross-fertilization." We also have stressed the indivisibility of the somatic and psychological processes in the indivisible continuum of human life from its very beginning and the inseparability of the development and functions of the central nervous system and the immunological and neuroendocrine processes. This transdisciplinary and integrative aspect of sciences and their entree in the twenty-first century is the true vision for our common efforts. Integration means also amalgamation, assimilation, blending, combining, incorporation, unification and harmony. This last mentioned, harmony, should be stressed and underlined specifically: a harmony between different views and approaches, between different methods and methodologies, different theories and practices. In order to undertake such a challenge, a new scientific theory and a common language is required, a language that would be understood across disciplines and would be able to assist in getting beyond semantic problems. The bridge between the immune system, neuroendocrinology and the rest of the central nervous system opens the gateway to more common understanding and acceptance across the disciplines. It is an umbrella for the endeavor that unites various scientific fields in their attempt to elucidate the processes of experience involved from the earliest stages of human life. This integration does cross over the different disciplines and diagnostic systems. It attaches theoretical and applied fields, basic research and clinical experience throughout the whole continuity of human life from conception and onwards. Integrated Psychoimmuno-Neuroendocrinology represents a unique opportunity for the primary prevention of psychological, emotional and physical disorders.

Journal Article↗

[Integration and intramolecular transposition of the TnBP3 Bordetella pertussis transposon in the Escherichia coli K-12 cells -- mutant for the phosphoenolpyruvate-dependent phosphotransferase system Hpr protein ].

Integration of a plasmid carrying the TnBP3 transposon of Bordetella pertussis into the chromosome of Escherichia coli and transpositions of the integrated structure within a chromosome in the wild-type and mutant cells ptsH devoid of the major Hpr protein of the phosphoenolpyruvate-dependent phosphotransferase system were studied. When transposed to a new chromosome site, the integrated structure was precisely (or almost precisely) excised from the metY gene sequence, which resulted in restoration of the Met+ phenotype. The integration and transposition events were only observed in the E. coli cells carrying the ptsH+ allele. The ptsH mutations inhibited integration and intramolecular transposition, which were restored after phenotypic or genetic suppression of the ptsH mutation. The intensity of the processes studied were suggested to depend on the integrity of a chain that ensures transferring of the phosphoryl residue by proteins of the phosphotransferase system in E. coli K12. The results obtained indicate that the ptsH mutants of E. coli can serve as the optimal host for cloning of fragments carrying repeated sequences of B. pertussis, which may apply to the repeated sequences of other microorganisms.

Bacterial Proteins↗

Development and testing of an assessment tool for integrated learning.

OBJECTIVE: Development of integrated questions for undergraduate medical students and assessing students' capability to retain and apply basic concepts in an integrated way. METHOD: Multiple choice questions, attempting to probe understanding and application of different concepts, affiliated with different subjects and topics, were developed. As a pilot these were administered to the students of third year and final year at the end of their certifying examinations as a mock test. The following year these questions were introduced in the continuous assessments and subsequently the certifying examinations (in third year) as 33% of the whole examination. Difficult indices, item analysis and internal consistency (alpha) were calculated for all the questions. RESULTS: The difficulty indices of integrated questions indicated that students found the integrated questions difficult. CONCLUSION: There was a significant change of distribution in terms of scoring for the integrated questions. Students' power to integrate showed reliable improvement when tested in the certifying examinations.

Analysis of Variance↗

[Siblings of children with cancer: integration of illness experiences into personal life history].

Based on the hypothesis that personal narratives help to cope people with stressful life events, 33 adult siblings of former childhood cancer patients were asked how they had experienced illness and treatment of their brother or sister. Analysis of the narratives was used to measure the integration of these experiences into personal biography. Good integration correlated positively with good body concepts. Siblings with good integration also scored lower for fatalistic health locus of control and perceived the illness retrospectively as more distressing than those with poor integration. In contrast, integration did not correlate with distress evoked by present feelings towards illness and therapy or by thoughts of a relapse or a personal cancer illness. The findings of this exploratory investigation may suggest that successful integration of the experiences associated with a brother's or sister's cancer is associated with a trustful relation to the own body and with the ability to accept painful feelings and to allow them to emerge. Assisting siblings of young cancer patients to create and maintain their personal narratives of their experiences can make an important contribution to coping.

Adaptation, Psychological↗

[Abnormal expression of hepatitis B virus sequences integrated in human hepatocellular carcinomas].

Although epidemiologic studies have clearly demonstrated the importance of the hepatitis B virus in the genesis of hepatocellular carcinoma, the molecular basis for this tumorigenic effect is still under debate. The finding of hepatitis B virus DNA integration into human liver DNA in many cases of hepatocellular carcinoma suggested that these integrated viral sequences may be involved in liver carcinogenesis. In an attempt to clarify this point, we studied 9 tumors which developed in non cirrhotic livers. All tumors contained viral integrations (ranging from 1 to 6 different integrants) and 4 showed abnormal hepatitis B virus mRNA (2.3 to 7.5 kilobases long). The analysis of the corresponding cDNAs revealed the existence of hybrid transcripts containing both genomic and viral sequences. In 2 cases, the viral-host junctions were mapped within the cohesive-end region of the hepatitis B virus genome leading to the production of a transcript encoding a 3' truncated X protein. In another case, the cellular sequences present in the co-transcript were located in 5' with respect to the hepatitis B virus sequences. This observation strongly suggests that, in this patient, integration took place near a cellular gene. Further analysis of this integrant should help in identifying the putative gene and its application in the development of the tumor. We conclude that the study of abnormal hepatitis B virus transcripts in liver tumors provides a positive approach to study the direct role of HBV in carcinogenesis as an insertional mutagen.

Carcinoma, Hepatocellular↗

[Integration of the delivery of health services].

In Mexico the Constitution defines the right to health care as a social right and, as such, confers to the state the guiding role in the access of the population to health services. Unfortunately, this constitutional principle has not been fully met. One of the reasons for this is the fragmentation of public action in health and the continuous postponement of the integration of health services. In this paper the conceptual and practical limits of integration of health services are discussed, using as starting point a brief diagnosis of inequity and fragmentation of the health system in Mexico. The doctrinaire principles of integration are also described, as well as its practical advantages and disadvantages. Finally, a typology of forms of integration and previous integration experiences in Mexico are discussed. In the concluding remarks the integration prospects for Mexico are analyzed.

Decision Trees↗

[Responsibilities of pediatric medicine in integrated rehabilitation of handicapped children in Bremen].

Integrated education of handicapped children in Bremen is both goal and method. In the case of infants (0-3 years old) integration means integrating the child into the family by working with and within the family; for pre-school children (3-6 years old) this means education with non-handicapped children in a pre-school setting; integration in school settings using various approaches is still a goal. Integrated education is understood as a multi-disciplinary approach with the necessary inclusion of sociopaediatric competencies. The contribution to the concept of integration by paediatricians in Bremen is presented in this article. The work described is viewed as a perfect fit for paediatricians in the Public Health Services if they have the necessary preliminaries in self-understanding and qualification.

Child↗

Resolution of sensory ambiguities for gaze stabilization requires a second neural integrator.

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

Animals↗

Correlated discharge among cell pairs within the oculomotor horizontal velocity-to-position integrator.

In the oculomotor system, temporal integration of velocity commands into position signals may depend on synaptic feedback among neurons of a bilateral brainstem cell assembly known as the "neural integrator." Both ipsilateral excitatory and contralateral inhibitory projections between eye position-related integrator cells are hypothesized as a substrate for positive feedback supporting integration. Presence of feedback interactions should be evident in cross-correlation functions of neuron pairs. Here, unilateral and bilateral paired recordings were obtained during fixation behavior from neurons in goldfish brainstem area I, a key element of the integrator. During fixations, discharge of most unilateral pairs, composed of cells with eye position sensitivities of the same sign, was positively correlated with lag of 0-10 msec (n = 11 of 14 significant). Typically, a very narrow peak (mean half-width <4 msec) near zero lag was observed. Discharge of bilateral pairs, composed of cells with position sensitivities of the opposite sign, was either negatively correlated with lag of 0-10 msec (n = 5 of 13 significant) or not correlated. Troughs in negative correlations always had minima between 3 and 5 msec lag. These results are consistent with the feedback hypothesis of temporal integration, highlighting excitation unilaterally and inhibition bilaterally. Absence of visual input did not weaken correlations, but other sources of correlated input extrinsic to area I were not ruled out. Triplet recordings revealed that unilateral pairwise correlations were primarily independent. Correlation between unilateral pairs systematically decreased with increasing eye position, demonstrating that synchrony is not necessary for persistent activity at high firing rates.

Action Potentials↗

[Clinical study on the treatment of severe acute pancreatitis by integrated traditional Chinese medicine and Western medicine].

OBJECTIVE: To sum up clinical experiences and formulate a new treatment program for the effective managment of severe acute pancreatitis(SAP) by integrated TCM and western medicine. METHODS: The therapeutic regimens and end results of 1376 cases of SAP in three periods were reviewed and analyzed. Period I (1980-1990) was characterized by early surgical intervention supplemented with integrated traditional Chinese and western medical therapy, period II (1991-1993) by integrated traditional Chinese and western medical therapy supplemented with surgery for early complications, and period III (1994-2003) by integrated traditional Chinese and western medical therapy supplemented with surgery for local infectious complications at a late stage in the course of disease. RESULTS: With use of integrated traditional Chinese and western medical therapy in the treatment of SAP, the proportion of surgical operation and the case-fatality rate kept declining in the three consecutive periods, the proportions of operation being 77.59%, 54.54% and 19.38%, and the case-fatality rates being 40.52%, 17.17% and 10.77%, respectively. CONCLUSION: Integrated TCM and western medicine is effective for most SAP cases, and surgery is indicated mainly for late complications such as necrotizing infection. Early surgery should be handled with more circumspection and strictness in most of the patients with SAP.

Adolescent↗

[Value of autologous chondrocyte transplantation in experimental cartilage defects reconstruction. Part III--Microscopic analysis of reconstructed cartilage thickness and integration with surrounding tissue].

UNLABELLED: Lack of cartilage vascularization is the reason of its low regenerative potential. The aim of this part of the study was microscopic evaluation of repair tissue thickness and its integration with surrounding cartilage, after autologous chondrocyte transplantation. MATERIAL AND METHODS: Repair of partial thickness cartilage defect (ICRS III(o) grade) on distal femur joint surface was evaluated (25 adolescent rabbits). Procedures were performed in two groups: I--autologous chondrocyte transplantation under periosteal flap, II--periosteal graft. Chondrocytes were isolated from the cartilage specimens by enzymatic digestion and cultured in vitro. The follow-up periods were established at 4, 8, 12 weeks. Repair tissue was evaluated microscopically according to modified O'Driscoll scale. RESULTS: In group I, 8 weeks after the procedure most of defects were filled with the newly formed tissue almost completely. Regenerate thickness after 4 and 12 weeks usually exceeded 1/2 of surrounding cartilage. In group II, 8 weeks after the procedure regenerate thickness amounted to at least 1/2 of surrounding cartilage, but 4- and 12-week observation revealed the decreased repair tissue thickness. In group I, 4 weeks after the procedure regenerative tissue was well integrated with surrounding cartilage, and this trait still gradually increased with time. In group II, there was partial integration or no integration of repair tissue with surrounding cartilage. CONCLUSION: Obtained results indicate, that tissue formed after autologous chondrocyte transplantation with use of periosteal flap was better in its thickness and integration with surrounding cartilage, as compared to tissue formed after use of periosteum alone. Autologous chondrocyte transplantation can not guarantee complete filling of the cartilage defect with the graft tissue and full integration with surrounding cartilage, without three-dimensional scaffold application.

Animals↗

Feasibility study of imaging of intraductal papillary mucinous tumors of the pancreas based on integral photography.

BACKGROUND/AIMS: The principle of integral photography was first proposed by Lippman in 1908. Recently, the three-dimensional display system based on the principle of integral photography was developed. It projects three-dimensional objects using a lens array called a fly's eye lens and photographic film. Some groups have used it for surgical navigation in brain surgery. In this study, we tried to generate integral photographic images of intraductal papillary mucinous tumors of the pancreas, and evaluated the feasibility of this method. METHODOLOGY: Five patients with an intraductal papillary mucinous tumor of pancreas were studied. We used MRI data as three-dimensional data. MRI data were acquired with a 1.5-T clinical imager (Signal.5; GE Medical Systems, U.S.A). We used multi-slab single-shot fast spin-echo sequences. Section thickness was between 2 and 3mm in the coronal plane. From these data, integral photographic images were generated on a liquid crystal display by a three-dimensional rendering algorithm. RESULTS: Three-dimensional images using the principle of integral photography could be generated in all 5 cases. We could recognize these images as three-dimensional images by slightly moving the viewpoint to up, down, left, and right. From these images, we were able to grasp the three-dimensional relationship between the tumor, bile duct, and pancreatic duct. Using these three-dimensional images, a variety of minimally invasive surgical procedures were performed for intraductal papillary mucinous tumor of the pancreas, more safely and speedily than formerly. CONCLUSIONS: The images based on integral photography are suitable for medical imaging and are useful for surgical planning.

Adenocarcinoma, Mucinous↗

Attitudes of school environment towards integration of HIV-positive pupils into regular classes and knowledge about HIV/AIDS: cross-sectional study.

AIM: To estimate the attitudes of teachers, parents, and pupils in primary schools towards the integration of HIV-positive pupils into regular schools, and their knowledge about HIV/AIDS. METHODS: Teachers (n=64), seventh and eight grade pupils (n=108), and their parents (n=124) from a big city and a small town in Croatia were examined by two specially designed instruments which measured their attitudes towards the integration of pupils with HIV/AIDS and knowledge about HIV/AIDS. RESULTS: All three populations showed positive attitudes towards the integration of children with HIV/AIDS into regular schools. A group of parents had lower attitude score (mean-/+standard deviation, 3.1-/+0.6) compared with teachers or pupils (3.5-/+0.4 and 3.4-/+0.4 respectively, P<0.001, ANOVA, and post hoc Tukey test). Knowledge about HIV/AIDS was high in all three groups. Pupils scored lower (8.2-/+4.1 out of maximum 15) than their teachers or parents (11.2-/+3.8 and 10.3-/+3.5 respectively, P<0.001). In all three subsamples, groups with higher level of education had more positive attitudes towards the integration of children with HIV/AIDS into regular schools as well as higher knowledge scores. No significant correlation was found between participants' attitudes and knowledge. CONCLUSION: School environment - teachers, pupils, parents - had generally positive attitudes towards the integration of HIV positive pupils and high level of knowledge about HIV/AIDS. Generally, parents showed less favorable attitudes than teachers and pupils and this may be a possible obstacle to the integration of HIV positive students into regular schools. There is obviously a need for a coordinated public intervention aimed at informing the public about HIV/AIDS.

Adolescent↗

[Analysis of nonlinear behavior in cardiac QRS-waves integral].

QRS-waves integral can reflect the activities of ventricular depolarization. In this paper are analyzed the nonlinear characters in QRS-waves integral: reconstructing state space with these integral signals after nonlinear noise reduction, calculating its attractor dimension and the largest Lyapunov exponents. With the results based on MIT-BIH database we proposed that QRS-waves integral is of chaos nature. When compased with HRV nonlinear analysis, QRS-waves integral analysis was found to be of more advantages in some cases such as premature ventricular contraction. This QRS-waves integral nonlinear analysis may be of use in evaluating clinical cardiac function.

Electrocardiography↗

Construction of integrated case environments.

The main goal of Computer-Aided Software Engineering (CASE) technology is to improve the entire software system development process. The CASE approach is not merely a technology; it involves a fundamental change in the process of software development. The tendency of the CASE approach, technically speaking, is the integration of tools that assist in the application of specific methods. In this sense, the environment architecture, which includes the platform and the system's hardware and software, constitutes the base of the CASE environment. The problem of tools integration has been proposed for two decades. Current integration efforts emphasize the interoperability of tools, especially in distributed environments. In this work we use the Brown approach. The environment resulting from the application of this model is called a federative environment, focusing on the fact that this architecture pays special attention to the connections among the components of the environment. This approach is now being used in component-based design. This paper describes a concrete experience in civil engineering and architecture fields, for the construction of an integrated CASE environment. A generic architectural framework based on an intermediary architectural pattern is applied to achieve the integration of the different tools. This intermediary represents the control perspective of the PAC (Presentation-Abstraction-Control) style, which has been implemented as a Mediator pattern and it has been used in the interactive systems domain. In addition, a process is given to construct the integrated CASE.

Journal Article↗

[Detection of the integration of human FIX (hFIX)on chromosomes of transgenic mice by fluorescence in situ hybridization].

Fluorescence in situ hybridization (FISH) was used to detect the integration of hFIX on chromosomes of transgenic mice from F1 to F4 generation in two strains. For transgenic mice, 98%-100% of metaphases and 85%-94% of interphases showed hybridization signal. For negative control mice,100% of metaphases and 95%-96% of interphases showed no hybridization signal. The results demonstrated that FISH developed to detect the integration sites of hFIX was high efficient and specific. The integration sites of the transgenic mice analyzed were both single but different between the two strains. The integration chromosomes can be found in the transgenic mice from F1 to F4 generation and the integration sites were the same as each of the strains,which indicated that the transgene was stably integrated and transmitted to offspring.

English Abstract↗

The integrated blood-collection system as a vehicle into complete clinical laboratory automation.

A rationale is offered and methodology illustrated for integrating the fundamental steps involved in the collection and processing of blood for laboratory evaluation. The approach taken in the development of these concepts and components greatly extends the possibilities of laboratory systems integration without upsetting established modalities. A prototype design of the integrated blood-collection system integrates blood collection, cellular separations, sample transfer to stable storage without chemical mediators, and sample presentation for chemical analysis (e.g., precision metering) while preserving patient identification. A sophisticated, multi-chambered blood-collection container is the site of all blood sample processing and transfer steps. This device is supported by a compact, robotic centrifuge of unique design and a transfer mechanism to facilitate sample delivery for analysis within a diagnostic instrument. The confluence of these individual components into a single integrated system provides the means to completely automate the processing of blood samples, after sample collection, eliminating all manual transfer steps and any external exposure of blood interfaces outside the diagnostic instrument. Configurational derivatives of the Integrated Blood-Collection System offer choice of skin or venipuncture procedure, rapid plasma extraction for micro- or macro-collected volumes, and sample delivery by either aspiration or direct metering of discrete 10-microL samples from the collection container. The skin-puncture configuration provides the opportunity within a single device to collect and process up to 500 microL of sample by capillarity from a skin prick.

Automation↗