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We report a male patient who developed an unusual periodic breathing. At presentation, the differential diagnosis at bedside between Cheyne-Stokes and primary hyperventilation syndrome was laborious, and the final verification was based on the result of capnography.
Patient-focused care is a new model of care delivery organized around the patient instead of the hospital structure. Care is provided by multi-disciplinary teams of healthcare workers on the patient care unit. As many services as possible are brought to the patient, rather than taking the patient to a decentralized department. Successful models have demonstrated increased operational efficiency and greater levels of satisfaction among patients, physicians, and staff members. Administrative tasks done in a variety of departments may be assigned to a member of the care team. Such tasks may include patient registration; insurance verification and financial arrangements; and medical record assembly, analysis, abstracting, and coding. Given the different educational levels and prior training administrative team members may have, careful consideration must be given to assignment of the medical record abstracting and coding functions. The quality of clinical data submitted by all providers in the US is critically important to the future of the nation's healthcare system. Under prospective payment systems, the accuracy of clinical data abstracting and coding has a significant impact on healthcare facilities. But the need for accurate clinical data goes beyond payment systems. As more and more clinical data are being captured and maintained in databases across the country, for uses that may be yet unknown, it is essential that such data be collected consistently and accurately. To assure the quality and validity of health information, only trained, experienced coders should abstract and code the data.(ABSTRACT TRUNCATED AT 250 WORDS)
The enzymes and receptors in parasites that can be qualified as targets for antiparasite chemotherapy should perform essential functions in the parasites and demonstrate some feasibility for selective inhibition. They can be tentatively identified through detailed analysis of various aspects of metabolisms in the parasites or elucidation of the mechanisms of action among proven antiparasitic agents. Preliminary verifications of these putative targets can be indicated by in vitro antiparasite activity of an inhibitor of the target. However, before a major long-term effort to pursue in-depth structure-activity analysis of the target is to be committed for specific inhibitor design, further validations of the target are essential to insure that future studies are not misguided. One old-fashioned approach to validate a target in the pharmaceutical industry is by correlating target inhibitions with antiparasitic activities among large numbers of drug derivatives. The results are often indicative but hardly ever conclusive. Another method is by comparing the putative drug targets between the drug-sensitive and the drug-resistant parasites for potential discrepancies. Unfortunately, the latter often result from indirect causes, such as reduced drug transport, instead of an alteration of the drug target itself. The third experimental approach is by disrupting the gene encoding the putative target in parasite, which can provide the most conclusive evidence on whether the target plays an indispensible role in the parasite. But special conditions are needed for the gene knockout mutants to survive to exhibit their phenotypes and to allow genetic complementation studies for further verifications. Furthermore, gene knockout experiments are often difficult to perform on cells of multiple ploidy or genes of multiple copies, and are currently applicable only to a limited number of protozoan parasites. In the current article I have tried to take a cursory look at some eleven putative drug targets among various parasites, each supported by well-established antiparasitic agents identified as its inhibitors. I have also considered the evidence for validity of each of them and the potential means of further verifying their validity.
A subpopulation of dogs of the Collie and Australian Shepherd breeds show increased sensitivity to central nervous actions of ivermectin, doramectin, loperamide, and probably several other drugs. The molecular background for this greater sensitivity is a nonsense mutation in the MDR1 efflux pump, which is part of the functional blood-brain barrier and normally limits drug penetration into the brain. This report describes a rapid PCR-based method for detection of this nt230(del4) MDR1 mutation using a small amount of genomic DNA from blood cells. Thereby, homozygous intact, homozygous mutated, and heterozygous mutated MDR1 genotypes can be clearly differentiated by high resolution polyacrylamide gel electrophoresis. Using this diagnostic test two Collies and one Australian Shepherd were screened for the nt230(del4) MDR1 mutation. The Collies had no history of altered drug sensitivity and showed homozygous intact and heterozygous mutated MDR1 alleles, respectively. However, the Australian Shepherd developed clear signs of neurotoxicity including ataxia, crawling, acoustic and tactile hyperexcitability, and miosis after a single dose of moxidectin (400 microg/kg). For this dog two mutated MDR1 alleles were detected. This report describes for the first time moxidectin neurotoxicosis in a dog with a homozygous MDR1 mutation.
We examined the relationship between brain activities and task performance on working memory. A large-scale study was initially administered to identify good and poor performers using the operation span and reading span tasks. On the basis of those span scores, we divided 20 consenting participants into high- and low-span groups. In an fMRI study, the participants performed verification of arithmetic problems and retention of target words either concurrently or separately. The behavioral results showed that performance was better in the high-span group than in the low-span group under a dual-task condition, but not under two single-task conditions. The anterior cingulate cortex (ACC), left prefrontal cortex (PFC), left inferior frontal cortex, and bilateral parietal cortex were primarily activated for both span groups. We found that signal changes in the ACC were greater in the high-span group than in the low-span group under the dual-task condition, but not under the single-task conditions. Structural equation modeling indicated that an estimate of effective connectivity from the ACC to the left PFC was positive for the high-span group and negative for the-low span group, suggesting that closer cooperation between the two brain regions was strongly related to working memory performance. We conclude that central executive functioning for attention shifting is modulated by the cingulo-frontal network.
BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) is an increasingly common treatment for Parkinson's disease. Qualitative reviews have concluded that diminished verbal fluency is common after STN DBS, but that changes in global cognitive abilities, attention, executive functions, and memory are only inconsistently observed and, when present, often nominal or transient. We did a quantitative meta-analysis to improve understanding of the variability and clinical significance of cognitive dysfunction after STN DBS. METHODS: We searched MedLine, PsycLIT, and ISI Web of Science electronic databases for articles published between 1990 and 2006, and extracted information about number of patients, exclusion criteria, confirmation of target by microelectrode recording, verification of electrode placement via radiographic means, stimulation parameters, assessment time points, assessment measures, whether patients were on levodopa or dopaminomimetics, and summary statistics needed for computation of effect sizes. We used the random-effects meta-analytical model to assess continuous outcomes before and after STN DBS. FINDINGS: Of 40 neuropsychological studies identified, 28 cohort studies (including 612 patients) were eligible for inclusion in the meta-analysis. After adjusting for heterogeneity of variance in study effect sizes, the random effects meta-analysis revealed significant, albeit small, declines in executive functions and verbal learning and memory. Moderate declines were only reported in semantic (Cohen's d 0.73) and phonemic verbal fluency (0.51). Changes in verbal fluency were not related to patient age, disease duration, stimulation parameters, or change in dopaminomimetic dose after surgery. INTERPRETATION: STN DBS, in selected patients, seems relatively safe from a cognitive standpoint. However, difficulty in identification of factors underlying changes in verbal fluency draws attention to the need for uniform and detailed reporting of patient selection, demographic, disease, treatment, surgical, stimulation, and clinical outcome parameters.
The HP CareVue system is an object-oriented, client-server system optimized for critical care, inpatient and special care environments. It is a fully graphical system, highly visual in its mode of operation, which requires no commands to operate. Data review may be performed by clinical users without specific instructions. Several different kinds of interfaces are provided for the system. These allow it to be connected to most hospital data-producing systems, physiologic monitors and bedside devices, such as ventilators, urimeters and oximeters. Flowsheet charting, free text, structured notes, clinical pathways, configurable forms, medication administration records and many other types of displays and reports allow the system to function as a nearly complete Electronic Medical Record (EMR). The system is highly configurable by lead nurses, physicians or technicians without programming knowledge or experience. Configuration and linking of multiple CareVue systems is possible, including a complete testing environment for verification of charting changes before clinical activation. All CareVue data is exportable for purposes of electronic archiving, warehousing and real-time decision support.
The general topic of computers and nuclear medicine quality control may be approached from two main areas; controlling the quality of computerized studies, and computer applications in general nuclear medicine quality control. Overlap occurs when quality control of computer studies is performed by the computer itself. The uses of computers in record-keeping and in quality control of imaging instrumentation and in vitro studies, including radioimmunoassay, are discussed in this review. Aspects of quality control for computerized clinical cardiovascular, cerebral, and renal studies and emission computed tomography are reviewed, including consideration of difficulties and inaccuracies involved in the studies. Any automatic computer analysis program should incorporate adequate checks and error detection protocols and should illustrate results for verification. Current routine quality control procedures using the computer unfortunately are few. Quality control criteria are needed for camera/computer systems in high count rate clinical applications, and increasing emphasis should be aimed at quality control of those computerized dynamic and function studies in current clinical use. The computer has a valuable potential for nuclear medicine quality control. In vitro and computerized in vivo studies can be analyzed by readily available statistical programs, and variances can be monitored continuously. Computers can calibrate and monitor instrument performance regularly, and can handle managerial and clerical duties such as bookkeeping.
By analogy to other cation channel subunits with six transmembrane-spanning domains, the seven members of the "classical" or "canonical" transient receptor potential channels (TRPC) family are believed to assemble into homo- or heterotetrameric complexes. These complexes have been verified by classical methods such as coimmunoprecipitation, crosslinking analysis or functional assays applying dominant negative pore mutants. More recently, fluorescence resonance energy transfer (FRET)-a measure for the close proximity of fluorescent molecules-has become instrumental in monitoring protein assembly in living cells. Here we demonstrate further possibilities and verification procedures of the FRET technology to test the assembly of ion channel subunits. Temporally and spatially resolved FRET imaging demonstrates an early assembly of TRPC subunits in the endoplasmic reticulum and the Golgi apparatus. Confocal FRET imaging verifies FRET signals over the plasma membrane at high spatial resolution. Taking advantage of the quantitative analysis of digital video imaging, we demonstrate that FRET between TRPC subunits is only poorly concentration-dependent. Moreover, a correlation between the efficiency of energy transfer and the molar ratio of the FRET donor to the acceptor was exploited to verify the tetrameric stoichiometry of TRPC complexes. Finally, we introduce a competition-FRET assay to test the ability of wild-type TRPC subunits to recruit fluorescent TRPC subunits into separate channel complexes.
Picture archival and communications systems (PACS) for radiation oncology present an entirely different set of constraints and requirements from systems developed for diagnostic imaging. PACS for radiation oncology aid in organizing the complex, interrelated functions of radiation oncology. Integration of PACS with clinical data management systems will provide the backbone for the comprehensive computer system that has long been sought in radiation oncology. Simulation, geometric and dosimetric treatment planning, field shaping, set-up, verification, and delivery are now all observable and/or controllable from computer systems that can be interfaced with the departmental PACS. Costs are substantially lower than with diagnostic PACS because the systems can be based on desktop computers and the image resolution requirements are not as stringent. Each PACS user will have more information more easily available than under current systems of organization. Vendor support of digital image communications (DICOM) protocols will enable full integration of equipment regardless of manufacturer. Potential increased in productivity will be realized if the systems for handling and evaluating images are fully automated and provide the users with analytic tools that enhance the utility of systems such as electronic portal imagers, multileaf collimators, and clinical data management systems. this report describes our efforts in producing such a system.
Proteomic approaches to biological research that will prove the most useful and productive require robust, sensitive, and reproducible technologies for both the qualitative and quantitative analysis of complex protein mixtures. Here we applied the isotope-coded affinity tag (ICAT) approach to quantitative protein profiling, in this case proteins that copurified with lipid raft plasma membrane domains isolated from control and stimulated Jurkat human T cells. With the ICAT approach, cysteine residues of the two related protein isolates were covalently labeled with isotopically normal and heavy versions of the same reagent, respectively. Following proteolytic cleavage of combined labeled proteins, peptides were fractionated by multidimensional chromatography and subsequently analyzed via automated tandem mass spectrometry. Individual tandem mass spectrometry spectra were searched against a human sequence database, and a variety of recently developed, publicly available software applications were used to sort, filter, analyze, and compare the results of two repetitions of the same experiment. In particular, robust statistical modeling algorithms were used to assign measures of confidence to both peptide sequences and the proteins from which they were likely derived, identified via the database searches. We show that by applying such statistical tools to the identification of T cell lipid raft-associated proteins, we were able to estimate the accuracy of peptide and protein identifications made. These tools also allow for determination of the false positive rate as a function of user-defined data filtering parameters, thus giving the user significant control over and information about the final output of large-scale proteomic experiments. With the ability to assign probabilities to all identifications, the need for manual verification of results is substantially reduced, thus making the rapid evaluation of large proteomic datasets possible. Finally, by repeating the experiment, information relating to the general reproducibility and validity of this approach to large-scale proteomic analyses was also obtained.
Intracellular recordings of membrane potentials of mudpuppy lingual cells were made with micropipette electrodes. Three types of cells were distinguished by their responses to chemical stimulation. Surface epithelial (SE) cells outside of taste buds responded with large membrane potential and resistance changes to a variety of stimuli representing the four taste qualities. Salts and acids evoked particularly large potential changes, and MgCl2, acids, and quinine greatly increased the membrane resistance. One type of taste bud cell (TB-1) was characterized by large depolarizations to K salts, and the other type of taste bud cell (TB-2) characteristically hyperpolarized to MgCl2, acid, and sugar solutions. Membrane resistance changes accompanying TB-1 and TB-2 cell responses were relatively small compared to those of SE cells. Electrotonic coupling was observed between pairs of SE and TB-2 cells but not for pairs of TB-1 cells nor cells of different types. After recording cell responses, dye-marking allowed verification of results in situ and histologically. From the identification of cells in section, it is hypothesized the TB-1 and TB-2 cells correspond to light and dark cells, respectively. Responses of TB-1 cells imply a taste receptive function; wheras TB 2-cell responses suggest secretory, supportive, and (or) receptive functions. Factors affecting cellular characteristics, non-taste bud cell responsiveness, response mechanisms, and function of electrotonic coupling are discussed in relation to taste reception.
Recent theory and research are reviewed regarding self-related motives (self-enhancement, self-verification, and self-expansion) and self-conscious emotions (guilt, shame, pride, social anxiety, and embarrassment), with an emphasis on how these motivational and emotional aspects of the self might be related. Specifically, these motives and emotions appear to function to protect people's social well-being. The motives to self-enhance, self-verify, and self-expand are partly rooted in people's concerns with social approval and acceptance, and self-conscious emotions arise in response to events that have real or imagined implications for others' judgments of the individual. Thus, these motives and emotions do not operate to maintain certain states of the self, as some have suggested, but rather to facilitate people's social interactions and relationships.
Hormone-dependent breast cancer responds to primary therapies that block estrogen production or action, but tumor regrowth often occurs 12-18 months later. Additional hormonal treatments that further reduce estrogen synthesis or more effectively block its action cause additional remissions, but the mechanisms responsible for these secondary responses are not well understood. As a working hypothesis, we postulated that primary hormonal therapy induces adaptive changes, resulting in enhanced estrogen receptor (ER) expression and target gene activation and, further, that secondary treatment modalities interfere with these receptor-mediated transcriptional pathways. To test this hypothesis, we used an MCF-7 breast cancer model system involving deprivation of estradiol in culture for a prolonged period. These long-term estradiol-deprived (LTED) cells adapt by acquiring the ability to regrow in the absence of added estradiol. The experimental paradigm involved the comparison of wild-type cells with LTED cells. As endpoints, we directly assessed ER expression at the messenger RNA-, protein-, and ligand-binding levels and ER functionality by quantitating reporter gene activation and expression of endogenous estrogen target gene messenger RNA, as well as ER coactivator levels. Our data demonstrated an adaptive increase in ER expression and in basal ER functionality, as assessed by read-out of three different transfected reporters in LTED, as opposed to wild-type MCF-7 cells. Increased reporter gene read-out was dramatically inhibited by the pure antiestrogen ICI 182,780. As verification that endogenous (as well as transfected) estrogen target genes had enhanced transcription, we found that the basal levels of c-myb and c-myc message were substantially increased in LTED cells and could be inhibited by antiestrogen. Interestingly, the levels of c-myb and c-myc message in the LTED cells seemed to be increased out of proportion to the degree of ER reporter gene activation and were similar to those in wild-type cells maximally stimulated with estradiol. In addition, not all estrogen-responsive genes were activated, because transforming growth factor-alpha message level was not increased in LTED cells. Up-regulation of the steroid receptor coactivator SRC-1 did not seem to mediate the process of enhanced ER-induced transcription. Considering these observations together, we suggest that long-term estradiol deprivation causes adaptive processes that not only involve up-regulation of the ER but also influence the specificity and magnitude of activation of estrogen-responsive genes.
PURPOSE: MicroRNAs (miRNAs) are capable of controlling gene expression by targeting complimentary sequences in many mRNAs. Thus, a small number of miRNAs are capable of regulating expression of many different genes. miRNAs have been found in all animals from Drosophila to human and they are highly conserved. This work was undertaken in order to identify such RNAs in the newt eye. METHODS: Cloning of these RNAs was attempted after isolating and fractionating total RNA from the adult newt eye. A gel slice ranging from about 15 to 30 nucleotides in length was cut and the extracted RNA was cloned after several processes involving reverse transcription and linker addition. For expression analysis and verification during the process of lens regeneration we used as a probe mir-124a. RESULTS: Several microRNAs, piRNAs and other small RNAS were identified. Some of them have eye specific gene targets in other species, but for many a function in the eye remains to be attributed. Expression of miR-124a showed an interesting regulation in the lens regeneration-competent dorsal iris. CONCLUSIONS: The cloned miRNAs and other small RNAs are the first to be reported for this animal and might bear significance in regulating processes that are unique to the newt eye, i.e., regeneration of the lens and retina.
A follow up study of 40 cases of optic chiasm gliomas is presented. Histological examination was obtained in 26 cases. All were bipolar spongioblastomas. Four of these were optic nerve gliomas, 17 chiasmatic gliomas and 19 invasive optohypothalamic tumors. The main clinical features are reviewed with special attention to endocrine disorders, including precocious puberty and diencephalic emaciation. Neurofibromatosis was present in 30%. Diagnostic difficulties are outlined, especially in chiasmatic tumors without optic nerve involvement: event with C T scan, the differential diagnosis with ectopic pinealomas, craniopharyngiomas and primary hypothalamic tumors, may be difficult. The operative mortality was 12% (3/25). All but one, had radiotherapy either alone or post operative. All four of the patients with unilateral optic nerve gliomas have a normal C T scan more than 10 years after treatment. Of the 17 patients with chiasmatic gliomas, 14 are alive with normal C T scan in 2 cases, and with reduction in size of the tumor in 7. Eleven of 19 patients with invasive gliomas are alive with diminished size of the tumor in 7. Improvement in visual acuity, reduction in size of tumor mass, persistent increase in size of non irradiated tumor and lack of recurrence of optic nerve glioma even with histological proven chiasmatic involvement is taken as evidence of the effect of radiotherapy. The sub frontal approach is emphasized for optic nerve and optic chiasm tumors: it provides direct surgical verification with the opportunity for complete removal, large biopsy, decompression of the optic foramina or cyst removal. Regarding secondary endocrine disorders, radiotherapy is discussed in children. If necessary it must be managed under careful evaluation of endocrine status, principally growth function.
Chinese bilinguals performed a delayed naming task, reading both Chinese characters and English words, while EEGs were recorded by a 128-channel system. Principle component analysis (PCA) of Event Related Potentials (ERP) from the onset of the stimulus suggested a temporal unfolding of graphic, phonological, and semantic processing that depended on both language and word frequency. At 150 msec, Chinese produced an earlier and higher amplitude shift (N150) than English. At 250 msec, frequency effects were significant for both Chinese and English, but at 450 msec, only the English frequency effect was reliable. Source localization analysis by Low Resolution Electromagnetic Tomography (LORETA) showed bilateral occipital (left BA 17, right BA 18) visual processing of Chinese characters with left occipital only (left BA 17) for English high-frequency words. Low-frequency English words showed activation bilaterally, but with a more diffused and extended temporal pattern. Right prefrontal area (BA 10) was found to be strongly activated in the mid latency (300-400 msec) period of Chinese character naming, whereas English word naming showed more medial frontal (BA 8, and 10) activation. A post 450-msec visual verification was found to be general for both writing systems.
Cultures of the nematode C. elegans were examined for the presence of calcium-dependent, phospholipid-binding proteins of the annexin class. A single protein of apparent mass on SDS-polyacrylamide gels of 32 kD was isolated from soluble extracts of nematode cultures on the basis of its ability to bind to phospholipids in a calcium-dependent manner. After verification of the protein as an annexin by peptide sequencing, an antiserum to the protein was prepared and used to isolate a corresponding cDNA from an expression library in phage lambda gt11. The encoded protein, herein referred to as the nex-1 annexin, has a mass of 35 kD and is 36-42% identical in sequence to 10 known mammalian annexins. Several unique modifications were found in the portions of the sequence corresponding to calcium-binding sites. Possible phosphorylation sites in the NH2-terminal domain of the nematode annexin correspond to those of mammalian annexins. The gene for this annexin (nex-1) was physically mapped to chromosome III in the vicinity of the dpy-17 genetic marker. Two other annexin genes (nex-2 and nex-3) were also identified in chromosome III sequences reported by the nematode genomic sequencing project (Sulston, J., Z. Du, K. Thomas, R. Wilson, L. Hillier, R. Staden, N. Halloran, P. Green, J. Thierry-Mieg, L. Qiu, et al. 1992. Nature (Lond.). 356:37-41). The nex-1 annexin was localized in the nematode by immunofluorescence and by electron microscopy using immunogold labeling. The protein is associated with membrane systems of the secretory gland cells of the pharynx, with sites of cuticle formation in the grinder in the pharynx, with yolk granules in oocytes, with the uterine wall and vulva, and with membrane systems in the spermathecal valve. The presence of the annexin in association with the membranes of the spermathecal valve suggests a novel function of the protein in the folding and unfolding of these membranes as eggs pass through the valve. The localizations also indicate roles for the annexin corresponding to those proposed in mammalian systems in membrane trafficking, collagen deposition, and extracellular matrix formation.