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Biomedical subjects

R Ng

Publications and source records attributed to R Ng.

At least 19 recordsLinked to original sources

Normal obstetric ultrasound reduces the risk of Down syndrome in fetuses of older mothers.

The objective of this study is to determine whether a normal fetal morphology ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We reviewed the results of amniocentesis and second trimester sonogram in all women older than 35 years from 1991 to 1995. None had prior screening. We excluded fetuses with structural anomalies. We determined the sensitivity and specificity of minor markers in detecting Down syndrome and also determined the reduction in risk of a normal sonogram. Among the 2060 women older than 35 years giving birth during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive testing but no second trimester sonogram, five had a normal sonogram and seven had one or more sonographic markers of Down syndrome. At least 17% of women older than 35 years did not participate in prenatal testing or ultrasound. Ultrasound detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45-72%), a false-positive rate of 10.6% (9.4-11.8%) and a positive predictor value of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal was 0.46 (0.31-0.61). In women older than 35 years, a normal second trimester sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of women older than 35 years do not participate in prenatal testing or ultrasound.

Adult↗

Correcting the anion gap for hypoalbuminaemia does not improve detection of hyperlactataemia.

BACKGROUND: An elevated lactate level reflects impaired tissue oxygenation and is a predictor of mortality. Studies have shown that the anion gap is inadequate as a screen for hyperlactataemia, particularly in critically ill and trauma patients. A proposed explanation for the anion gap's poor sensitivity and specificity in detecting hyperlactataemia is that the serum albumin is frequently low. This study therefore, sought to compare the predictive values of the anion gap and the anion gap corrected for albumin (cAG) as an indicator of hyperlactataemia as defined by a lactate > or =2.5 mmol/l. METHODS: A retrospective review of 639 sets of laboratory values from a tertiary care hospital. Patients' laboratory results were included in the study if serum chemistries and lactate were drawn consecutively. The sensitivity, specificity, and predictive values were obtained. A receiver operator characteristics curve (ROC) was drawn and the area under the curve (AUC) was calculated. RESULTS: An anion gap > or =12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 79%, and 58%, respectively, and a cAG > or =12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 59%, 66%, and 69%, respectively. The ROC curves between anion gap and cAG as a predictor of hyperlactataemia were almost identical. The AUC was 0.757 and 0.750, respectively. CONCLUSIONS: The sensitivities, specificities, and predictive values of the anion gap and cAG were inadequate in predicting the presence of hyperlactataemia. The cAG provides no additional advantage over the anion gap in the detection of hyperlactataemia.

Acid-Base Equilibrium↗

Near patient blood ketone measurements and their utility in predicting diabetic ketoacidosis.

AIM: To assess the utility of near patient blood ketone measurements in predicting diabetic ketoacidosis (DKA) among a group of hyperglycaemic unwell patients presenting to a hospital emergency department. METHODS: Near patient blood beta-hydroxybutyrate (beta-OHB) testing has recently been introduced as a new tool in our hospital Accident and Emergency department (A&E) for patients with a finger-prick glucose of > 11 mmol/l. We reviewed the records of the first 50 patients to have a beta-OHB measurement to establish if they developed DKA or received treatment with intravenous insulin within 48 h of presentation. We then compared the diagnostic power of beta-OHB measurements with other clinical, physiological and biochemical markers of DKA. RESULTS: Nine patients had DKA, eight had a compensated metabolic acidosis secondary to raised serum ketones, and 33 had no evidence of DKA during the following 48 h. The median (range) beta-OHB levels in each group were 6.0 (3.1-6.0) mmol/l, 3.4 (1.2-5.7) mmol/l, and 0.1 (0.0-1.2) mmol/l, respectively. A beta-OHB level of > or = 3.0 mmol/l had a sensitivity of 100% and specificity of 88% for DKA. All those with beta-OHB level > 3.0 mmol/l required treatment with intravenous insulin. CONCLUSION: Measuring beta-OHB when a hyperglycaemic patient is identified could offer a simple method of identifying at an early stage those patients at highest risk of DKA (beta-OHB > 3.0 mmol/l), and redirecting the search for a diagnosis in others (beta-OHB < 1.0 mmol/l).

3-Hydroxybutyric Acid↗

Is hemifacial microsomia linked to multiple maternities?

Hemifacial microsomia describes a congenital orofacial malformation in which there is insufficient or disrupted development of the mandible affecting one side of the face. The aetiology of this condition remains unclear, but it has been postulated that twins (predominantly monozygotic) are more liable to be affected than singletons. This study investigates the incidence of multiple births amongst a large number of affected individuals and their families. Data were collected on 145 individuals with hemifacial microsomia and microtia, using postal questionnaires and interviews in a hospital setting. These data were compared with the mean age-standardised twin maternity prevalence for England and Wales between 1975 and 1995 of 1.06% and the triplet maternity prevalence for England and Wales for 1995 of 0.034% (a multiple maternity being where more than one baby is born, either alive or stillborn). The prevalence of twin maternities amongst the affected individuals was 3.96% (P>0.05) and amongst their siblings it was 4.02% (P<0.02). There was also an excess of twins in the rest of the family groups, predominantly due to a stronger history of twinning on the maternal side. As there were more twins amongst the affected individuals than in the general population, it seems likely that whatever the aetiology of hemifacial microsomia and microtia, the presence of a co-twin (or co-triplets) may make the causal event, or series of causal events, more likely to occur. This study supports the hypothesis that hemifacial microsomia and microtia are in some way linked to multiple births. Analysis of this link may provide new directions for research into the aetiology of a variety of congenital defects.

Diseases in Twins↗

Age differences in social preferences among Taiwanese and Mainland Chinese: the role of perceived time.

Socioemotional selectivity theory holds that as people recognize the inevitable constraint of time imposed by mortality, their social goals change, motivating them to limit social contacts to those with whom they are emotionally close. This theory was tested among Taiwanese and Mainland Chinese. As predicted, results showed that older adults (aged 60-90 years) in both cultures were more likely than younger adults (aged 18-30 years) to prefer familiar social partners who were most likely to provide emotionally close social interactions. Mainland Chinese, who as a group have shorter actuarial life expectancy, were more likely to prefer familiar social partners than were Taiwanese. These age and cultural differences were eliminated when differences in perceived time were statistically controlled for.

Adult↗

Preferential expression of antioxidant response element mediated gene expression in astrocytes.

Transcriptional control of target genes by antioxidant/electrophile response elements has been well described in peripheral tissues. Genes that are regulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone oxidoreductase, gamma-glutamyl cystine synthetase and glutathione-S-transferase. Antioxidant/electrophile response elements within a gene's promoter confer induction by low-molecular-weight electrophilic compounds such as tert-butylhydroquinone and dimethyl fumarate. We have now examined the ability of antioxidant/electrophile response elements to elicit gene expression in neurons and astrocytes in both brain slices and primary cultures using transient transfection of promoter reporter constructs. Our results using a heat-stable human placental alkaline phosphatase reporter indicate that antioxidant/electrophile response element mediated gene expression is largely restricted to astrocyte cell populations. Placental alkaline phosphatase expression was significantly elevated in astrocytes treated with the antioxidant/electrophile response element inducer dimethyl fumarate. Mutant constructs lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest that astrocytic metabolic processes that normally aid and/or protect neurons may be controlled via this inducible system.

Animals↗

Suppression of the accumulation of triosephosphates and increased formation of methylglyoxal in human red blood cells during hyperglycaemia by thiamine in vitro.

The accumulation of triosephosphates and the increased formation of the potent glycating agent methylglyoxal in intracellular hyperglycaemia are implicated in the development of diabetic complications. A strategy to counter this is to stimulate the anaerobic pentosephosphate pathway of glycolysis by maximizing transketolase activity by thiamine supplementation, with the consequent consumption of glyceraldehyde-3-phosphate and increased formation of ribose-5-phosphate. To assess the effect of thiamine supplementation on the accumulation of triosephosphates and methylglyoxal formation in cellular hyperglycaemia, we incubated human red blood cell suspensions (50% v/v) in short-term culture with 5 mM glucose and 50 mM glucose in Krebs-Ringer phosphate buffer at 37 degrees C as models of cellular metabolism under normoglycaemic and hyperglycaemic conditions. In hyperglycaemia, there is a characteristic increase in the concentration of the triosephosphate pool of glycolytic intermediates and a consequent increase in the concentration and metabolic flux of the formation of methylglyoxal. The addition of thiamine (50-500 microM) increased the activity of transketolase, decreased the concentration of the triosephosphate pool, decreased the concentration and metabolic flux of the formation of methylglyoxal, and increased the concentration of total sedoheptulose-7-phosphate and ribose-5-phosphate. Biochemical changes implicated in the development of diabetic complications were thereby prevented. This provides a biochemical basis for high dose thiamine therapy for the prevention of diabetic complications.

Deoxyglucose↗

Internet use amongst New Zealand general practitioners.

AIMS: To assess how extensively New Zealand doctors are using medical information on the Internet, and to examine how the new technology is affecting their practice of medicine. METHODS: All general practitioners (GPs) known to be working in Otago and Southland were asked to complete a postal questionnaire regarding their use of the Internet and their impressions of patient use of online medical resources. RESULTS: Of 259 questionnaires mailed out, 168 (65%) were returned by GPs currently in practice. Of those, 114 (68%) said they used the Internet at least monthly. A total of 71% of GPs had patients who indicated they had sought medical information from the Internet. Nearly half of respondents expressed concerns that the Internet could have unwelcome effects on the doctor-patient relationship. CONCLUSIONS: Internet use among New Zealand doctors and patients is widespread, and is likely to have significant impact on medical practice now and in the future. While the potential benefits of the new technology are numerous, the Internet may become a source of conflict between doctors and patients.

Data Collection↗

Eradication of human non-Hodgkin's lymphoma in SCID mice by BCL-2 antisense oligonucleotides combined with low-dose cyclophosphamide.

Cancers overexpressing Bcl-2 protein, which prevents programmed cell death (apoptosis), are less sensitive to stresses that produce cellular damage, including chemotherapy. If the level of Bcl-2 protein can be reduced sufficiently using antisense oligonucleotides (ASOs) targeting the gene message, then cytotoxic agents may be rendered more effective in eliminating disease and increasing cure rate. Preclinical studies in SCID mice bearing Bcl-2 overexpressing systemic human B-cell lymphoma (DoHH2) were undertaken to support development of a clinical trial. These data confirm that a combination of an ASO (5 mg/kg) targeting bcl-2 and a low dose of cyclophosphamide (35 mg/kg) was an effective strategy, leading to the eradication of the DoHH2 cells in vivo and cure of the animals. When mice deficient in natural killer cell activity were treated with an ASO, similar results were observed, suggesting that ASO stimulation of the host immune system was not a significant factor in elimination of lymphoma cells. These studies indicate that therapeutic strategies involving the use of an ASO targeting bcl-2 in combination with a cytotoxic agent may improve clinical outcomes.

Animals↗

Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P<.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

Adolescent↗

Close relationships and adjustment to a life crisis: the case of breast cancer.

When life crises occur, significant others are thought to help alleviate distress and resolve practical problems. Yet life crises may overwhelm significant others, eroding their ability to provide effective support. The accuracy of these contrasting accounts of relationship functioning was evaluated in a study of 102 breast cancer patients and their significant others, interviewed at 4 and 10 months after diagnosis. Results largely confirmed the negative account of relationship functioning. Although significant others provided support in response to patients' physical impairment, they withdrew support in response to patients' emotional distress. Moreover, support from significant others did not alleviate patients' distress or promote physical recovery. These results reveal limits to the effectiveness of close relationships in times of severe stress.

Activities of Daily Living↗

Neutralization of endogenous IL-6 suppresses induction of IL-1 receptor antagonist.

IL-1 is a potent cytokine that promotes host defense and inflammation. These processes may be modulated by an IL-1 receptor antagonist (IL-1Ra) that binds to and blocks IL-1 receptors. The objective of this study was to define the cellular origin and regulation of IL-1Ra production during bacterial infection. Oral infection of mice with Yersinia enterocolitica resulted in expression of IL-1Ra mRNA and synthesis of IL-1Ra in Peyer's patches (PP), the local site of infection, as well as in noninfected organs such as spleens. By immunostaining, recruited circulating neutrophils were identified to be the primary source of IL-1Ra in tissues. Only approximately 20% of the IL-1Ra-staining cells were accounted for by inflammatory macrophages. Strikingly, neutralization of IL-6 by anti-IL-6 antiserum caused a suppression of both IL-1Ra mRNA in PP and synthesis of IL-1Ra in circulating neutrophils. Confirmatory evidence that IL-6 participates in the generation of IL-1Ra was obtained when rIL-6 induced, and anti-IL-6 antiserum blocked, IL-1Ra expression in cultures of macrophage and polymorphonuclear leukocytes (PMN). These findings suggest that IL-6 induced induction of IL-1Ra may provide a negative feedback loop, facilitating resolution of the inflammatory response locally and presumably at remote sites of infection.

Animals↗

Effect of growth hormone on bone marrow grafts in fracture healing--an experimental study in rabbits.

The lack of effectiveness of growth hormone in stimulating the healing of fresh fractures has been attributed to the presence of insufficient precursor osteogenic cells at the fracture site for the growth hormone to exert its influence. We tested the effect of growth hormone on healing in a rabbit non-union model after injection of autogenous marrow cells into the fracture gap. Two millilitres of bone marrow were injected percutaneously into 1 cm diaphyseal defects of rabbit radii. The test group was given subcutaneous human recombinant growth hormone at 0.3 IU/kg/day in divided doses for 2 weeks, while the control group received subcutaneous saline injections. Biomechanical, radiological and callus calcium content assessments were carried out at 4 and 7 weeks. There was significantly increased tensile strength and callus calcium concentration in the group given growth hormone both at 4 and 7 weeks but there was no significant difference in stiffness or in callus volume in the 2 groups. These data suggest that growth hormone can enhance the osteogenic potential of bone marrow as a graft in the treatment of fracture non-union.

Animals↗

Behaviour disorder in pre-school children in Hong Kong. A two-stage epidemiological study.

A representative sample of 855 Hong-Kong Chinese children aged 36-48 months were assessed using the BSQ and the PBCL. Good reliability for both instruments were found. For the BSQ and PBCL, 12.75% and 27.5% were above the cut-off points of 10+ and 12+ respectively and 5.9% were above both cut-off points. In the second stage, 234 subjects were recruited by stratified random sampling according to the results of the screening state. A clinician interviewed the parent, child and teacher before making a diagnosis. The prevalence of behaviour disorder was: nil, 53.7%; dubious, 23.1%; mild, 18.0%; moderate, 4.5%; and severe, 0.7%. There were significantly more boys in the categories mild, moderate and severe.

Adult↗

Mutational and in vitro protein-binding studies on centromere DNA from Saccharomyces cerevisiae.

Centromeres on chromosomes in the yeast Saccharomyces cerevisiae contain approximately 140 base pairs (bp) of DNA. The functional centromere (CEN) region contains three important sequence elements (I, PuTCACPuTG; II, 78 to 86 bp of high-AT DNA; and III, a conserved 25-bp sequence with internal bilateral symmetry). Various point mutations or deletions in the element III region have a profound effect on CEN function in vivo, indicating that this DNA region is a key protein-binding site. This has been confirmed by the use of two in vitro assays to detect binding of yeast proteins to DNA fragments containing wild-type or mutationally altered CEN3 sequences. An exonuclease III protection assay was used to demonstrate specific binding of proteins to the element III region of CEN3. In addition, a gel DNA fragment mobility shift assay was used to characterize the binding reaction parameters. Sequence element III mutations that inactivate CEN function in vivo also prevent binding of proteins in the in vitro assays. The mobility shift assay indicates that double-stranded DNAs containing sequence element III efficiently bind proteins in the absence of sequence elements I and II, although the latter sequences are essential for optimal CEN function in vivo.

Base Sequence↗

Correlation of fibrinolytic activity with invasion and metastasis of R3230 AC rat mammary carcinoma cell lines.

The parent R3230 AC rat mammary carcinoma cell line and the two variant cell lines, R3230 AC MET and R3230 AC LR, differ with respect to their abilities to invade bony matrices and to form lung colonies (experimental metastases). Both the R3230 AC and the R3230 AC MET, a cell line selected in vivo for enhanced metastatic capability, express high potentials for invasiveness and lung colony formation, while the Con A- and WGA-resistant R3230 AC LR cell line grows expansively at the periosseus implantation site and is unable to form lung colonies after intravenous inoculation. The abilities to invade bone and to metastasize to the lung are well correlated with the fibrinolytic activity and the production of urokinase-type plasminogen activators. The contribution of plasminogen activators to invasiveness and metastasis has been ascribed to its role in the fibrinolytic and collagenolytic (i.e., activation of latent collagenase) cascades.

Animals↗