Clinical features and predictors for mortality in a designated national SARS ICU in Singapore.
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Comorbidity↗
Biomedical subjects
S Loo
Publications and source records attributed to S Loo.
Severe hyperphosphataemia and associated electrolyte and metabolic derangement following the administration of sodium phosphate for bowel preparation.
Sodium phosphate is widely used as an effective bowel preparation agent. It is used in smaller volumes, leading to improved patient tolerance. Although it is generally safe, cases of severe hyperphosphataemia following sodium phosphate administration have been reported in the literature. The common risk factors identified are advanced age, impaired renal function, impaired colonic motility and multiple doses. However, many doctors remain unaware of the dangers associated with this agent. We report six cases of severe electrolyte and metabolic derangement due to sodium phosphate bowel preparation: two patients had delayed awakening from general anaesthesia, and four patients suffered life-threatening consequences.
Age Factors↗
Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study.
BACKGROUND: Herbal remedies used by patients for treatment of inflammatory bowel disease include slippery elm, fenugreek, devil's claw, Mexican yam, tormentil and wei tong ning, a traditional Chinese medicine. Reactive oxygen metabolites produced by inflamed colonic mucosa may be pathogenic. Aminosalicylates (5-ASA) are antioxidant and other such agents could be therapeutic. AIMS: To assess the antioxidant effects of herbal remedies in cell-free oxidant-generating systems and inflamed human colorectal biopsies. METHODS: Luminol-enhanced chemiluminescence in a xanthine/xanthine oxidase cell-free system was used to detect superoxide scavenging by herbs and 5-ASA, and fluorimetry to define peroxyl radical scavenging using a phycoerythrin degradation assay. Chemiluminescence was used to detect herbal effects on generation of oxygen radicals by mucosal biopsies from patients with active ulcerative colitis. RESULTS: Like 5-ASA, all herbs, except fenugreek, scavenged superoxide dose-dependently. All materials tested scavenged peroxyl dose-dependently. Oxygen radical release from biopsies was reduced after incubation in all herbs except Mexican yam, and by 5-ASA. CONCLUSIONS: All six herbal remedies have antioxidant effects. Fenugreek is not a superoxide scavenger, while Mexican yam did not inhibit radical generation by inflamed biopsies. Slippery elm, fenugreek, devil's claw, tormentil and wei tong ning merit formal evaluation as novel therapies in inflammatory bowel disease.
Adult↗
Vascular endothelial growth factor-D (VEGF-D) is an endothelial hyperpermeability inducing growth factor differentially expressed in human cardiac allografts.
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Journal Article↗
Use of en face silver nitrate staining to assess endothelial gaps and vascular permeability in rat coronary artery transplant vasculopathy.
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Journal Article↗
Neonatal neurological testing in resource-poor settings.
The aim of the study was to design and test a neurological examination for newborns that could be performed reliably by paramedical staff in resource-poor settings. The examination was adapted from a method established by Dubowitz et al., the latest version of which includes an optimality score. The final items in the test were chosen because they were culturally acceptable, could be elicited according to strict but easily comprehensible instructions and because the expected responses could be scored by the descriptions given or by diagrams in the proforma. The shortened examination was easily taught to paramedical staff who achieved a high degree of inter-observer reliability. This shortened version of the examination was piloted by comparing newborns from a Karen refugee camp on the western border of Thailand and from a large maternity hospital in Bangkok with a standardized cohort of newborns in London. The modified shortened version of the test was sufficiently sensitive to identify a number of differences between the cohorts, notably the poor vision performance and markedly reduced tone of the Karen newborns. In conclusion, the test can be used very reliably by paramedical staff and is a useful, simple and portable tool for the neurological assessment of newborn babies where resources are limited.
Allied Health Personnel↗
Role of neutrophils and alpha1-antitrypsin in coal- and silica-induced connective tissue breakdown.
Mineral dusts produce emphysema, and administration of dust to rats results in the rapid appearance of desmosine and hydroxyproline in lavage fluid, confirming that dusts directly induce connective tissue breakdown. To examine the role of neutrophils and alpha1-antitrypsin (alpha1-AT) in this process, we instilled silica or coal into normal rats or rats that had been pretreated with antiserum against neutrophils. One day after dust exposure, lavage fluid neutrophils and desmosine and hydroxyproline levels were all elevated; treatment with antiserum against neutrophils reduced neutrophils by 75%, desmosine by 40-50%, and hydroxyproline by 25%. By 7 days, lavage fluid neutrophils and desmosine level had decreased, whereas macrophages and hydroxyproline level had increased. By ELISA analysis, lavage fluid alpha1-AT levels were increased four- to eightfold at both times. On Western blot, some of the alpha1-AT appeared as degraded fragments, and by HPLC analysis, 5-10% of the methionine residues were oxidized. At both times, lavage fluid exhibited considerably elevated serine elastase inhibitory capacity and also showed elevations in metalloelastase activity. We conclude that, in this model, connective tissue breakdown is initially driven largely by neutrophil-derived proteases and that markedly elevated levels of functional alpha1-AT do not prevent breakdown, thus providing in vivo support for the concept of quantum proteolysis proposed by Liou and Campbell (T. G. Liou and E. J. Campbell. Biochemistry 34: 16171-16177, 1995). Macrophage-derived proteases may be of increasing importance over time, especially in coal-treated animals.
Animals↗
The use of magnesium sulphate in the intensive care management of an Asian patient with tetanus.
Tetanus, a potentially fatal but largely preventable disease through immunisation, is rare in Singapore. Timely diagnosis and appropriate intensive care management is essential to ensure survival. We aim to report the management of such a patient with magnesium sulphate. This has not been reported locally. By maintaining serum magnesium at 3 to 4 mmol/l we were able to control sympathetic overactivity by day 6, stop neuromuscular blockade by day 7 and wean off ventilator by day 11. Aminoglycoside-induced hypomagnesemia was also demonstrated, necessitating an increase in magnesium sulphate infusion rate to maintain serum magnesium at therapeutic level.
Adult↗
The origin recognition complex, SIR1, and the S phase requirement for silencing.
Silencing of transcription in Saccharomyces cerevisiae has several links to DNA replication, including a role for the origin recognition complex (ORC), the DNA replication initiator, in both processes. In addition, the establishment of silencing at the HML and HMR loci requires cells to pass through the S phase of the cell cycle. Passage through S phase was required for silencing of HMR even under conditions in which ORC itself was no longer required. The requirement for ORC in silencing of HMR could be bypassed by tethering the Sir1 protein to the HMR-E silencer. However, ORC had a Sir1-independent role in transcriptional silencing at telomeres. Thus, the role of ORC in silencing was separable from its role in initiation, and the role of S phase in silencing was independent of replication initiation at the silencers.
Aldose-Ketose Isomerases↗
Infection in central lines: antiseptic-impregnated vs standard non-impregnated catheters.
We report a survey of 196 consecutive central venous catheters (CVCs) placed in 151 patients in the Intensive Care Unit (ICU) over a ten-month period. Over this time the use of a new antiseptic-impregnated triple lumen CVC (Arrowgard Blue, Arrow International Inc., Pennsylvania, U.S.A.) was alternated on a bimonthly basis with the standard triple-lumen CVC (Arrow International Inc., Pennsylvania, U.S.A.). The overall rate of CVC tip infection was lower in the impregnated CVC group (15.6% vs 30.9%, P < 0.05). The impregnated CVC group had a much lower cumulative infection rate when the dwell time in patients was five days or less (3.3% vs 26.9%, P < 0.05). However, the difference between the cumulative infection rate was not statistically significant (P > 0.05) for dwell times of 6, 7 or 8 days respectively. There was no difference in the CVC related bacteraemia rates between the two groups (3.9% vs 3.7%, P > 0.05).
Adolescent↗
Perioperative transfusion strategies: a national survey among anaesthetists.
A current concern in perioperative transfusion therapy is the balance between maintaining adequate haemoglobin level and yet avoiding unnecessary homologous blood transfusion. Strategies to minimise the perioperative use of homologous blood include redefining the traditional transfusion trigger of "10/30 rule", and the use of autologous transfusion therapy. Current recommendations for transfusion triggers advocate determining the "minimum acceptable haemoglobin level" for patients according to various other physiological or surgical factors. The current status of practice amongst anaesthetists in the above mentioned transfusion strategies was assessed using a national survey. An overall response rate of 59.4% was obtained. Results showed wide variation among respondents in their criteria used for preoperative and intraoperative transfusion. Recommendations on perioperative transfusion triggers made by various authors were also summarised. Autologous transfusion therapy was also not frequently practised-the reasons for this were identified. We concluded that in order to continually improve on the anaesthetic community's quality of perioperative care, continued education on the subject must be carried out. Certain practical issues also need to be addressed to facilitate the use of perioperative autologous transfusion therapy.
Anesthesia↗
Methylphenidate and attentional training. Comparative effects on behavior and neurocognitive performance in twin girls with attention-deficit/hyperactivity disorder.
The effectiveness of four doses (5-mg, 10-mg, 15-mg, 20-mg) of methylphenidate (MPH) and attentional training (AT) were evaluated using neurocognitive instruments (Continuous Performance Test; Matching Unfamiliar Figures Test), narrow- and broad-band rating scales in the context of a double-blind, placebo-control, within-subject reversal design for dizygotic twin girls with Attention-Deficit/Hyperactivity Disorder (ADHD). Both interventions proved effective for improving neurocognitive test performance and behavior, although broad-band ratings revealed dose-response curves different from those obtained from the neurocognitive tests. Implications for clinical management of girls with ADHD are discussed.
Attention↗
The origin recognition complex has essential functions in transcriptional silencing and chromosomal replication.
The role of the origin recognition complex (ORC) was investigated in replication initiation and in silencing. Temperature-sensitive mutations in ORC genes caused defects in replication initiation at chromosomal origins of replication, as measured by two-dimensional (2-D) origin-mapping gels, fork migration analysis, and plasmid replication studies. These data were consistent with ORC functioning as a eukaryotic replication initiator. Some origins displayed greater replication initiation deficiencies in orc mutants than did others, revealing functional differences between origins. Alleles of ORC5 were isolated that were defective for silencing but not replication, indicating that ORC's role in silencing could be separated from its role in replication. In temperature-sensitive orc mutants arrested in mitosis, temperature-shift experiments caused a loss of silencing, indicating both that ORC had functions outside of the S phase of the cell cycle and that ORC was required for the maintenance of the silenced state.
Cell Cycle↗
The origin recognition complex in silencing, cell cycle progression, and DNA replication.
This report describes the isolation of ORC5, the gene encoding the fifth largest subunit of the origin recognition complex, and the properties of mutants with a defective allele of ORC5. The orc5-1 mutation caused temperature-sensitive growth and, at the restrictive temperature, caused cell cycle arrest. At the permissive temperature, the orc5-1 mutation caused an elevated plasmid loss rate that could be suppressed by additional tandem origins of DNA replication. The sequence of ORC5 revealed a potential ATP binding site, making Orc5p a candidate for a subunit that mediates the ATP-dependent binding of ORC to origins. Genetic interactions among orc2-1 and orc5-1 and other cell cycle genes provided further evidence for a role for the origin recognition complex (ORC) in DNA replication. The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes.
Amino Acid Sequence↗
Roles of ABF1, NPL3, and YCL54 in silencing in Saccharomyces cerevisiae.
A sensitized genetic screen was carried out to identify essential genes involved in silencing in Saccharomyces cerevisiae. This screen identified temperature-sensitive alleles of ORC2 and ORC5, as described elsewhere, and ABF1, NPL3, and YCL54, as described here. Alleles of ABF1 that caused silencing defects provided the genetic proof of Abflp's role in silencing. The roles of Npl3p and Ycl54p are less clear. These proteins did not act exclusively through any one of the three protein binding sites of the HMR-E silencer. Unlike the orc2, orc5, and abf1 mutations that were isolated in the same (or a similar) screen for silencing mutants, neither temperature-sensitive mutation in NPL3 or YCL54 caused overt replication defects.
Alleles↗
Silencing and heritable domains of gene expression.
Silencing is a process that assembles particular regions of eukaryotic chromosomes into transcriptionally inactive chromatin structures. Silencing involves specialized regulatory sites known as silencers and a combination of general DNA-binding proteins and proteins dedicated to silencing. In the yeast Saccharomyces cerevisiae, these proteins include transcription factors and the origin recognition complex (ORC). Silencing has three recognizably separate phases: establishment, maintenance, and inheritance. At least some silencers are origins of replication, and the establishment of the silenced state requires an S phase-specific event. Once established, the silenced state is heritable, even in the absence of proteins required for its establishment. The silencing of mating-type genes bears many similarities to telomere position effects, and the two processes require many of the same proteins.
Alleles↗
Silencers and domains of generalized repression.
Gene expression can be affected by the chromosomal position of the gene. An example of this position effect is silencing of the HML and HMR mating-type loci of Saccharomyces cerevisiae. An in vitro assay revealed that silencing induced a transcription-independent general occlusion of the DNA at HMR from sequence-specific interactions of proteins with DNA. The minimum boundaries of the silenced chromatin structure were determined, as were the contributions of the E and I silencers to the size of the silenced domain. Examination of endonuclease-sensitive sites provided evidence that neither the integrity of the chromosomal duplex nor covalent linkage of the silencers to HMR was important for maintenance of the silenced structure in vitro.
Cell Nucleus↗
Regulation of Saccharomyces cerevisiae CDC7 function during the cell cycle.
The yeast Cdc7 function is required for the G1/S transition and is dependent on passage through START, a point controlled by the Cdc28/cdc2/p34 protein kinase. CDC7 encodes a protein kinase activity, and we now show that this kinase activity varies in the cell cycle but that protein levels appear to remain constant. We present several lines of evidence that periodic activation of CDC7 kinase is at least in part through phosphorylation. First, the kinase activity of the Cdc7 protein is destroyed by dephosphorylation of the protein in vitro with phosphatase. Second, Cdc7 protein is hypophosphorylated and inactive as a kinase in extracts of cells arrested at START but becomes active and maximally phosphorylated subsequent to passage through START. The phosphorylation pattern of Cdc7 protein is complex. Phosphopeptide mapping reveals four phosphopeptides in Cdc7 prepared from asynchronous yeast cells. Both autophosphorylation and phosphorylation in trans appear to contribute to this pattern. Autophosphorylation is shown to occur by using a thermolabile Cdc7 protein. A protein in yeast extracts can phosphorylate and activate Cdc7 protein made in Escherichia coli, and phosphorylation is thermolabile in cdc28 mutant extracts. Cdc7 protein carrying a serine to alanine change in the consensus recognition site for Cdc28 kinase shows an altered phosphopeptide map, suggesting that this site is important in determining the overall Cdc7 phosphorylation pattern.
Amino Acid Sequence↗