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Incidence of hypotension and bradycardia during integrated epidural/general anaesthesia. An epidemiologic observational study on 1200 consecutive patients. Italian Study Group on Integrated Anaesthesia.

BACKGROUND: Combined epidural/general anaesthesia might theoretically emphasise the cardiovascular effects of epidural block alone. The goal of the present investigation was to evaluate the incidence of both hypotension and bradycardia during integrated epidural/general anaesthesia in a multicentric, observational study. METHODS: The incidence of clinical hypotension (systolic arterial blood pressure decrease by 30% or more from baseline), and bradycardia (heart rate < 50 beats/min) and other side effects have been evaluated in 1200 consecutive patients receiving integrated epidural/general anaesthesia. The time from induction of epidural anaesthesia to induction of general anaesthesia was considered as preoperative; while the time after general anaesthesia induction was considered as intraoperative. RESULTS: Preoperatively hypotension developed in 85 patients (2.8%), and bradycardia in 54 patients (4.5%). Intraoperatively, hypotension was observed in 380 patients (31.6%), and bradycardia in 153 patients (12.7%). Hypotension and bradycardia were not influenced by the type of surgical procedure, the type of maintenance of general anaesthesia (inhalational versus total intravenous general anaesthesia) and the level of epidural block (lumbar versus thoracic); but they were more frequent in patients with ASA physical status II and III-IV compared to patients with ASA physical status I (p < 0.05). Prophylactic volume preload decreased the incidence of hypotension from 41.5% to 22.4% (p < 0.0001), while prophylactic atropine before epidural block did not affect the incidence of bradycardia. Patients receiving epidural clonidine showed an increased incidence of intraoperative bradycardia compared to those who did not receive it (p < 0.0001). DISCUSSION: Randomized, controlled studies should be advocated in order to compare the incidence of hypotension and bradycardia during integrated anaesthesia and during epidural block alone. Our results demonstrated that the use of integrated epidural/general anaesthesia produces an incidence of perioperative hypotension and bradycardia similar to that reported when central blocks are used alone.

Adult↗

Managing clinical integration in integrated delivery systems: a framework for action.

An integrated delivery system (IDS) in healthcare must coordinate patient care across multiple functions, activities, and operating units. To achieve this clinical integration, senior management confronts many challenges. This paper uses a cross-functional-process (CFP) framework to discuss these challenges. There are ten CFPs that fall into three categories: planning processes (strategy formulation, program adaptation, budget formulation), organizational processes (authority and influence, client management, conflict resolution, motivation, and cultural maintenance), and measurement and reporting processes (financial and programmatic). Each process typically spans several functional units. Senior management must consider how to improve both the functioning of each CFP, as well as its "fit" with the other nine. The result can be greater clinical integration, improved cost management, and more coordinated care for enrollees.

Budgets↗

The challenge of integrating clinical information systems in an integrated delivery system.

The development and implementation of the information systems necessary to support an effective and efficient continuum of care and to measure the quality and cost of that care present complex information systems integration challenges. The article discusses the integration challenges and concludes with a review of strategies that an integrated delivery system can adopt to begin to address them.

Computer Systems↗

Forced integration of Moloney murine leukemia virus DNA with a mutant integration site occurs through recombination with VL30 DNA.

The integration of retroviral DNA to form the provirus requires the presence of short inverted repeat sequences at the termini of the linear viral DNA. We have previously described the construction of a mutant of Moloney murine leukemia virus, carrying an 8-bp deletion in the U5 terminus, that is defective in establishing the integrated provirus. We have now used a selectable marker to allow recovery of rare proviruses formed after transduction from NIH/3T3 cells by retroviral vectors carrying this mutation. Analysis of two such proviruses showed that both were recombinants between the vector and VL30 DNA and arose such that the VL30 sequences could provide an intact terminal sequence for integration.

3T3 Cells↗

Integration site for Streptomyces phage phiBT1 and development of site-specific integrating vectors.

Despite extensive similarities between the genomes of the Streptomyces temperate phages phiC31 and phiBT1, the attP-int loci are poorly conserved. Here we demonstrate that phiBT1 integrates into a different attachment site than phiC31. phiBT1 attB lies within SCO4848 encoding a 79-amino-acid putative integral membrane protein. Integration vectors based on phiBT1 integrase were shown to have a broad host range and are fully compatible with those based on the phiC31 attP-int locus.

Amino Acid Sequence↗

A technique for genome-wide identification of differences in the interspersed repeats integrations between closely related genomes and its application to detection of human-specific integrations of HERV-K LTRs.

We have developed a method of targeted genomic difference analysis (TGDA) for genomewide detection of interspersed repeat integration site differences between closely related genomes. The method includes a whole-genome amplification of the flanks adjacent to target interspersed repetitive elements in both genomic DNAs under comparison, and subtractive hybridization (SH) of the selected amplicons. The potential of TGDA was demonstrated by the detection of differences in the integration sites of human endogenous retroviruses K (HERV-K) and related solitary long terminal repeats (LTRs) between the human and chimpanzee genomes. Of 55 randomly sequenced clones from a library enriched with human-specific integration (HSI) sites, 33 (60%) represented HSIs. All the human-specific (Hs) LTRs belong to two related evolutionarily young groups, suggesting simultaneous activity of two master genes in the hominid lineage. No deletion/insertion polymorphism was detected for the LTR HSIs for 25 unrelated caucasoid individuals. We also discuss the possible research applications for TGDA research.

Animals↗

Integration of scientific criteria into the psychotherapy integration movement.

Psychotherapy integration has recently received considerable attention among behavior therapists. Although the wisdom of ecumenicism has been questioned, behavior therapy has often been credited with flexibility and modification of practice based on experimental and clinical research. From this perspective, the two central criteria for psychotherapy integration are inclusion of proven therapeutic elements and exclusion of unproven ones. Rationales for the importance of both criteria are discussed, and an analogy to the development of modern medicine is suggested. Formal acceptance of the proposed criteria would place psychotherapy integration in a proactive position to censor fee-for-service clinical practice not grounded in basic clinical or experimental research.

Behavior Therapy↗

Retroviral DNA integration: structure of an integration intermediate.

The structure of a presumptive DNA intermediate in the integration of retroviral DNA was studied in a cell-free reaction with exogenously added target DNA. The product made by viral core particles of Moloney murine leukemia virus (Mo-MLV) containing linear viral DNA has a structure consistent with an integration mechanism similar to that observed during bacteriophage Mu transposition. In this intermediate, the 3' ends of the LTR sequences are joined to the target DNA, while the 5' ends of the viral DNA remain unjoined. The 5' ends of the LTR sequences in the intermediate are exactly the same as those found in the unintegrated linear double-stranded viral DNA. This result demonstrates that the linear form of Mo-MLV DNA can integrate directly without prior circularization.

Cell-Free System↗

Monolithically integrated bacteriorhodopsin/semiconductor opto-electronic integrated circuit for a bio-photoreceiver.

The light-sensitive protein, bacteriorhodopsin (BR), is monolithically integrated with an InP-based amplifier circuit to realize a novel opto-electronic integrated circuit (OEIC) which performs as a high-speed photoreceiver. The circuit is realized by epitaxial growth of the field-effect transistors, currently used semiconductor device and circuit fabrication techniques, and selective area BR electro-deposition. The integrated photoreceiver has a responsivity of 175 V/W and linear photoresponse, with a dynamic range of 16 dB, with 594 nm photoexcitation. The dynamics of the photochemical cycle of BR has also been modeled and a proposed equivalent circuit simulates the measured BR photoresponse with good agreement.

Amplifiers, Electronic↗

Osmotic tolerance limits and effects of cryoprotectants on the motility, plasma membrane integrity and acrosomal integrity of rat sperm.

Osmotic stress is an important factor that can result in cell damage during cryopreservation. The objectives of this study were to determine: (1) isosmotic sperm cell volume; (2) osmotically inactive volume; (3) osmotic tolerance limits of rat sperm; and (4) the effects of addition and removal of glycerol (Gly), ethylene glycol (EG), propylene glycol (PG) or dimethyl sulfoxide (Me(2)SO) on rat sperm function. Sperm from Fischer 344 and Sprague-Dawley rats were used in this study. An electronic particle counter was used to measure the cell volume of rat sperm. Computer-assisted sperm motility analysis and flow-cytometric analysis were used to assess sperm motility, plasma membrane and acrosomal integrity. The isosmotic sperm cell volumes of the two strains were 37.0+/-0.1 and 36.2+/-0.2 microm(3), respectively. Rat sperm behaved as linear osmometers from 260 to 450 mOsm, and the osmotically inactive sperm volumes of the two strains were 79.8+/-1.5% and 81.4+/-2.2%, respectively. Rat sperm have very limited osmotic tolerances. The sperm motility and the sperm plasma membranes of both strains were sensitive to anisosmotic treatments, but the acrosomes of both strains were more sensitive to hyposmotic than hyperosmotic conditions. The one-step addition and removal of Me(2)SO showed the most deleterious effect on rat sperm motility, plasma membrane integrity, and acrosomal integrity among the four cryoprotectants. These data characterizing rat sperm osmotic behavior, osmotic and cryoprotectant tolerance will be used to design cryopreservation protocols for rat sperm.

Acrosome↗

Cerebral atrophy measurements using Jacobian integration: comparison with the boundary shift integral.

We compared two methods of measuring cerebral atrophy in a cohort of 38 clinically probable Alzheimer's disease (AD) subjects and 22 age-matched normal controls, using metrics of zero atrophy, consistency, scaled atrophy and AD/control group separation. The two methods compared were the boundary shift integral (BSI) and a technique based on the integration of Jacobian determinants from non-rigid registration. For each subject, we used two volumetric magnetic resonance (MR) scans at baseline and a third obtained 1 year later. The case of zero atrophy was established by registering the same-day baseline scan pair, which should approximate zero change. Consistency was established by registering the 1-year follow-up scan to each of the baseline scans, giving two measurements of atrophy that should be very similar, while scaled atrophy was established by reducing one of the same-day scans by a fixed amount, and rigidly registering this to the other same-day scan. Group separation was ascertained by calculating atrophy rates over the two 1-year measures for the control and AD subjects. The results showed the Jacobian integration technique was significantly more accurate in calculating scaled atrophy (P < 0.001) and was able to distinguish between control and AD subjects more clearly (P < 0.01).

Aged↗

Brain activity related to integrative processes in visual object recognition: bottom-up integration and the modulatory influence of stored knowledge.

We report evidence from a PET activation study that the inferior occipital gyri (likely to include area V2) and the posterior parts of the fusiform and inferior temporal gyri are involved in the integration of visual elements into perceptual wholes (single objects). Of these areas, the fusiform and inferior temporal gyri were more activated by tasks with recognizable stimuli than by tasks with unrecognizable stimuli. We propose that the posterior parts of the fusiform and inferior temporal gyri, compared with the inferior occipital gyri, are involved in higher level integration, due to the involvement of re-entrant activation from stored structural knowledge. Evidence in favor of this interpretation comes from the additional finding that activation of the anterior part of the left fusiform gyrus and a more anterior part of the right inferior temporal gyrus, areas previously associated with access to stored structural knowledge, was found with recognizable stimuli, but not with unrecognizable stimuli. This latter finding also indicates: (i) that subjects may not refrain from (automatically) identifying objects even if they only have to attend to the objects' global shape, and (ii) that perceptual and memorial processes can be dissociated on both functional and anatomical grounds. No evidence was obtained for the involvement of the parietal lobes in the integration of single objects.

Adult↗

Transcription of integrated MMTV LTR DNA in fibroblast clones is not associated with DNA methylation but with the integration site.

By transfecting 3T3 TK- fibroblasts with a plasmid DNA containing the MMTV LTR promotor and the thymidine kinase gene, we have isolated TK+ clones that contain only one copy of the recombinant DNA. The newly acquired DNA is integrated at different sites in each TK+ clones and can be amplified as a tandem repeat in some cases. The basal level of expression of the newly acquired LTR sequence is variable among the TK+ clones studied. Among those producing detectable amounts of MMTV RNA, we found that transcription is initiated from the LTR promotor and that the synthesis is stimulated by a short dexamethasone treatment. In addition, the presence of tandem repeated LTR DNA does not amplify the MMTV RNA synthesis. Endogenous LTR sequences have been found to be methylated, whereas we show that the newly integrated sequences, both as single copy and tandem repeats, remain unmethylated. Thus, non-methylation of MMTV LTR DNA is necessary but not significant to allow its transcription. Our results suggest that the level of LTR promotor activity could be modulated by the nature of its integration site within the cellular genome.

Animals↗

An integrated CMOS microluminometer for low-level luminescence sensing in the bioluminescent bioreporter integrated circuit.

We report an integrated CMOS microluminometer for the detection of low-level bioluminescence in whole cell biosensing applications. This microluminometer is the microelectronic portion of the bioluminescent bioreporter integrated circuit (BBIC). This device uses the n-well/p-substrate junction of a standard bulk CMOS IC process to form the integrated photodetector. This photodetector uses a distributed electrode configuration that minimizes detector noise. Signal processing is accomplished with a current-to-frequency converter circuit that forms the causal portion of the matched filter for dc luminescence in wide-band white noise. Measurements show that luminescence can be detected from as few as 4 x 10(5) cells/ml.

Biosensing Techniques↗

Integrated CMOS photodetectors and signal processing for very low-level chemical sensing with the bioluminescent bioreporter integrated circuit.

We report an integrated CMOS microluminometer optimized for the detection of low-level bioluminescence as part of the bioluminescent bioreporter integrated circuit (BBIC). This microluminometer improves on previous devices through careful management of the sub-femtoampere currents, both signal and leakage, that flow in the front-end processing circuitry. In particular, the photodiode is operated with a reverse bias of only a few mV, requiring special attention to the reset circuitry of the current-to-frequency converter (CFC) that forms the front-end circuit. We report a sub-femtoampere leakage current and a minimum detectable signal (MDS) of 0.15 fA (1510 s integration time) using a room temperature 1.47 mm2 CMOS photodiode. This microluminometer can detect luminescence from as few as 5000 fully induced Pseudomonas fluorescens 5RL bacterial cells.

Biosensing Techniques↗

Response tempo and separable--integral responding: evidence for an integral-to-separable processing sequence in visual perception.

Three experiments were conducted to examine the relation between response tempo and separable-integral responding. A restricted classification paradigm, in which similarity-based (integral) and dimensionally based (separable) classifications were pitted against one another, was used with the dimensions of length and density (all experiments) and size and brightness (Experiment 3). The subjects were college students (Experiments 1 and 2) and kindergarten, second-, and fifth-grade children (Experiment 3). In all three experiments, rapid responding was associated with fewer dimensional and more similarity responses than was slow responding. This result held when response tempo was simply measured (Experiments 1 and 3) and when it was manipulated by the experimenter (Experiment 2). The results were interpreted to be consistent with models of dimensional processing in which holistic, integral processing precedes analytic dimensional processing.

Child↗

DNA rearrangement associated with the integration of T-DNA in tobacco: an example for multiple duplications of DNA around the integration target.

Transferred DNA (T-DNA) of the tumor-inducing (Ti) plasmid is transferred from Agrobacterium tumefaciens to plant cells and is stably integrated into the plant nuclear genome. By the inverse polymerase chain reaction DNA fragments were amplified that contained the T-DNA/plant DNA junctions from the total DNA of a transgenic tobacco plant that had a single copy of the T-DNA in a repetitive region of its genome. A DNA fragment containing the target site was amplified from the total DNA of non-transformed tobacco by the polymerase chain reaction using high-stringency conditions. Comparison of the nucleotide sequence of the target site with those of the T-DNA/plant DNA junctions revealed that various duplications of short stretches of nucleotide sequences around the target and in the incoming T-DNA had accompanied the integration of the T-DNA. A deletion of 16 bp at the target site was also found and the target site was similar, in terms of nucleotide sequence, to regions around the breakpoints of the T-DNA. This finding provides a clear example of the occurrence of complex rearrangements during the integration of T-DNA.

Agrobacterium tumefaciens↗

Multipole-based integral estimates for the rigorous description of distance dependence in two-electron integrals.

We derive multipole-based integral estimates (MBIE) as rigorous and tight upper bounds to four-center two-electron integrals in order to account for the 1/R distance decay between the charge distributions, which is missing in the Schwarz screening commonly used in ab initio methods. Our screening criteria are valid for all angular momenta and can be formulated for any order of multipoles. We have found the expansion limited to dipoles to be sufficiently tight for estimating the integrals in Hartree-Fock and density-functional theories, while the screening effort is negligible. For, e.g., a DNA fragment with 1052 atoms and 10,674 basis functions (6-31G*) the exchange part is faster by a factor of 2.1 as compared to the Schwarz screening both within our linear exchange scheme, whereas a smaller factor of 1.3 is gained for the Coulomb part within the continuous fast multipole method. Most importantly, our new MBIE screening is perfectly suited to exploit the strong distance decay of electron-correlation effects of at least 1/R4 in atomic-orbital-based formulations of correlation methods.

Journal Article↗