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Biomedical subjects

W Lim

Publications and source records attributed to W Lim.

At least 37 records · Page 2Linked to original sources
PubMed2000

Voltage-dependent K(+) currents in spiral prominence epithelial cells of rat cochlea.

It has been suggested that spiral prominence is associated with ion transport, but the characterization of ion channels has not been explored so far. We studied the electrical properties and ion conductances of the spiral prominence epithelial cells (SPECs), which are epithelial cells covering the luminal side of spiral prominence, in the upper turn of neonatal rat cochlea using a whole-cell variant patch clamp technique. The cell capacitance was 16.3+/-2.1 pF (n=33) and the resting membrane potential was -68. 9+/-2.5 mV (n=14) in perilymph-like bath solution. It was found that those SPECs possess a large voltage-activated, outwardly rectifying K(+) current and a small inwardly rectifying K(+) current. The outward K(+) current was activated by depolarizing pulses more positive than -30 mV, and sensitive to tetraethylammonium chloride (20 mM), 4-aminopyridine (10 mM), but not to Ba(2+) (0.5 mM). Tail current analysis revealed that it was primarily K(+)-selective. The time course of activation was well fitted by an exponential function raised to second power. The small inwardly rectifying K(+) current was sensitive to Ba(2+) (0.5 mM), and the Ba(2+)-sensitive current was K(+)-selective. In cell-attached or inside-out patch recordings, no discernible K(+) channel currents were found in the apical membrane of SPECs. Based on these results, we conclude that SPECs have two types of voltage-dependent K(+) currents, which are most likely located in the basolateral membrane.

Animals↗
PubMed2000

Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong.

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

Adult↗
PubMed2000

HIV-1 infected women and prenatal care utilization: barriers and facilitators.

In an effort to understand issues affecting prenatal care access and utilization from the perspectives of human immunodeficiency virus (HIV)-infected women who receive inadequate prenatal care, we conducted three in-depth qualitative and quantitative interviews. From a thematic analysis of the narrative interviews, four broad areas emerged as pertinent to these women's prenatal care experiences. These were issues related to pregnancy, HIV, psychosocial conditions, and the health care system. For these women, the barriers to prenatal care utilization included the unexpected and unplanned nature of the pregnancy and mental health issues related to HIV infection. Poverty, periodic homelessness, addiction to illicit substances, and lack of social support were also important barriers. Furthermore, perceptions of the health care system as threatening, including fears related to consequences of disclosing illicit activities, discrimination, and breach of confidentiality emerged as salient barriers. Facilitating factors included the pregnancy being experienced as a life-transforming event, concern for their children, especially preventing HIV-1 vertical transmission, availability of treatment, and support from health care professionals. Prominent throughout the interviews were the women's mental health concerns and need for professional support.

Adult↗
PubMed2000

Evolutionary characterization of the six internal genes of H5N1 human influenza A virus.

The entire nucleotide sequences of all six internal genes of six human H5N1 influenza A viruses isolated in Hong Kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2. The presence of previously reported amino acid sequences specific for human strains was confirmed in the PB2, PA, NP and M2 proteins. Nucleotide and amino acid sequence identities of the six internal genes of H5N1 viruses examined here were separated into at least two variant groups. In agreement with the above result, phylogenetic trees of the six internal genes of human H5N1 viruses were generally composed of two minor clades. Additionally, variable dendrogram topologies suggested that reassortment among viruses contributed further to the genetic variability of these viruses. As a result, it became clear that human H5N1 viruses are characterized by divergent gene constellations, suggesting the possible occurrence of genetic reassortment between viruses of the two evolutionary lineages.

DNA-Directed RNA Polymerases↗
PubMed1999

Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998.

Influenza A (H5N1) viruses infected humans in Hong Kong between May and December, 1997. Sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. Molecular analysis of the surface proteins genes encoding the hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype not previously known to infect humans, are presented. The 16 human H5 HA sequences contain multiple basic amino acids adjacent to the cleavage site, a motif associated with highly pathogenic avian influenza A viruses. The phylogenetic relationship among both avian and human H5 hemagglutinins indicates that the human isolates are related directly to isolates that circulated among chickens in the live poultry markets in Hong Kong prior to and during the outbreak in humans. HA sequences from the human isolates and a recent chicken isolate represent a separate clade, within which there are two subgroups that are distinguishable antigenically and by the presence of a potential glycosylation site. Likewise the N1 neuraminidases of the human H5 isolates represent a clade that is evolutionarily distinct from previously characterized N1 neuraminidases. The recent human H5N1 virus NA genes are avian-like, indicating direct introduction from an avian source rather than evolution of a human N1 NA. All of the 16 human NA genes encode a shortened stalk due to a 19-amino acid deletion, also found in the recent avian H5N1 isolates from Hong Kong. Two unique amino acids were identified in the N1 NAs of the recent human isolates; however, it is not known if these residues influence host range. Neither the HA nor the NA genes of the human H5N1 virus isolates show evidence of adaptive changes during the outbreak. Although analyses of the surface protein genes of the H5N1 viruses from this outbreak did not provide immediate answers regarding the molecular basis for virulence, the analyses provided clues to potentially important areas of the genes worth further investigation.

Adolescent↗
PubMed1999

Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina.

Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997. Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997. The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005). None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine.

Anti-HIV Agents↗
PubMed1999

Antibody response in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts.

The first documented outbreak of human respiratory disease caused by avian influenza A (H5N1) viruses occurred in Hong Kong in 1997. The kinetics of the antibody response to the avian virus in H5N1-infected persons was similar to that of a primary response to human influenza A viruses; serum neutralizing antibody was detected, in general, >/=14 days after symptom onset. Cohort studies were conducted to assess the risk of human-to-human transmission of the virus. By use of a combination of serologic assays, 6 of 51 household contacts, 1 of 26 tour group members, and none of 47 coworkers exposed to H5N1-infected persons were positive for H5 antibody. One H5 antibody-positive household contact, with no history of poultry exposure, provided evidence that human-to-human transmission of the avian virus may have occurred through close physical contact with H5N1-infected patients. In contrast, social exposure to case patients was not associated with H5N1 infection.

Adolescent↗
PubMed1999

Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.

From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.

Adolescent↗
PubMed1998

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

Amino Acid Sequence↗
PubMed1998

High prevalence of hepatitis C virus genotype 6 among certain risk groups in Hong Kong.

The genotype of hepatitis C virus (HCV) of 172 HCV-RNA positive serum specimens taken from patients with chronic liver diseases, thalassaemia major, chronic renal failure (CRF), haemophilia and intravenous drug abusers (IVDA) was determined by analysis of the amplified 5'UTR region by genotype-specific oligonucleotide probes and restriction fragment length polymorphism (RFLP). Six different genotypes and subtypes (1a, lb, 2, 3, 4 and 6) were found. Genotype lb was the predominant genotype among patients with chronic liver diseases (69.6%), followed by genotype 6 (18.8%), which was similar to that reported for blood donors in earlier studies. Pronounced differences in the distribution of genotypes were seen between the four risk groups. Patients with CRF had a similar distribution to those with chronic liver diseases, whilst the greatest diversity of genotypes was seen in patients with haemophilia, which was expected since they were given factor VIII manufactured overseas. Genotype 6 was particularly prominent in patients with thalassaemia major (50%) and IVDA (62.5%). It is possible that clonal spread of HCV genotype 6 has taken place among a closed subset of the population in Hong Kong through intravenous drug abuse.

Female↗
PubMed1998

Labour ward midwifery staff epidural knowledge and practice.

A survey was conducted amongst labour ward midwives at our hospital to evaluate education, knowledge and attitudes toward the management of epidural analgesia in labour. Sixty of 80 distributed forms were returned, giving a 75% response rate. Forty-two per cent of respondents had more than ten years' practice experience. Only 51% achieved a predetermined pass score for knowledge about epidural analgesia. Though most had received formal education about epidural analgesia, 35% felt postgraduate education was insufficient. A majority of midwives supported epidural analgesia on demand (78%), during established labour (74%), or for women at increased risk of caesarean section (82%). Midwives with lower knowledge levels were more likely to recommend epidural analgesia early in labour to multiparous women (P = 0.001) and to women with either a small or a large baby (P = 0.06). The majority of midwives (93%, 70% and 65%) would "almost always" top-up women with cardiac or medical diseases, multiple pregnancy or hypertensive disease, respectively. A clear requirement for ongoing education, with input from the anaesthetic department, was identified, irrespective of personal experience. Practice patterns are discussed and recommendations made with respect to improvement of epidural analgesia management and continuing education.

Adult↗
PubMed1998

Obstetricians' knowledge and attitudes toward epidural analgesia in labour.

A survey of all registered obstetrician/gynaecologists in Western Australia (n = 79) was conducted to obtain information regarding their level of knowledge about epidural analgesia (EA) in labour and its complications, their sources of information about EA, and their opinions regarding its role in labour and effect on progress of labour. Response rate was 68%. Most respondents had only received lectures about EA after specialist training and 20% did not achieve an adequate knowledge score. Those of less than five years' experience achieved significantly better scores. Over a third did not favour EA in labour until active labour was established, though 90% would recommend it by late first stage in those with a potentially complicated delivery. For women with cardiac or significant medical disease aggravated by labour, 18% would wait until the late first or second stage before suggesting EA. Seventy-seven per cent believed EA prolonged the second stage of labour, though opinion varied regarding EA effects on the duration and progress of first and third stages. Up to thirty minutes delay before epidural placement is acceptable to 87%. This survey suggests that there is both a demand and a need for greater education about EA in labour, particularly with respect to EA side-effects, complications and effects on labour, in the subgroup of obstetricians who have been in obstetric practice more than five years.

Adult↗
PubMed1997

Sera from amyotrophic lateral sclerosis patients reduce high-voltage activated Ca2+ currents in mice dorsal root ganglion neurons.

This study investigated the effects of sera from amyotrophic lateral sclerosis (ALS) patients on high voltage activated (HVA) Ca2+ current in mice dorsal root ganglion (DRG) cells using whole-cell voltage-clamp method. Mice were injected with sera from healthy adults, from patients with other neurological diseases, and from patients with the sporadic form of ALS, for a period of 3 days. Sera from five of six ALS patients reduced HVA Ca2+ current amplitude. The peak Ca2+ current was significantly reduced by ALS sera while the sera from healthy adults and patients with other diseases did not alter Ca2+ current. The inactivation kinetics was altered by ALS sera, and the half-inactivation voltage shifted to more negative potential in ALS group. These results suggest that sporadic ALS serum factors may exert interactions with the HVA Ca2+ channel in DRG cells to reduce the Ca2+ current.

Adult↗
PubMed1997

Ca2+-channel-dependent and -independent inhibition of exocytosis by extracellular ATP in voltage-clamped rat adrenal chromaffin cells.

Membrane currents and capacitance were measured to examine the effects of extracellular ATP on exocytosis in voltage-clamped rat adrenal chromaffin cells. ATP reversibly inhibited Ca2+ current (ICa) and exocytosis. The dependency of exocytosis on ICa evoked by 1-s depolarizations was determined. However, inhibition of exocytosis was 2.6 times larger than that estimated from the reduction of ICa, implying the existence of a Ca2+-channel-independent pathway. This inhibition did not rely on a further reduction of the intracellular Ca2+ concentration spike. ATP reduced the rate of exocytosis induced by clamping the intracellular Ca2+ concentration. Pertussis toxin blocked the inhibitory effects of ATP on ICa and exocytosis. Although RB-2, a P2Y antagonist, blocked the inhibitory effect of ATP on ICa, RB-2 itself produced large increase or decrease in membrane capacitance. Adenosine inhibited ICa via a pertussis-toxin-sensitive pathway but did not significantly inhibit exocytosis. Our data show that extracellular ATP inhibits exocytosis via inhibition of ICa by activation of a pertussis-toxin-sensitive G-protein linked to P2Y receptors. Furthermore, our data strongly suggest that ATP activates another pathway, which is also G-protein dependent and accounts for the majority of the inhibitory effect of ATP on exocytosis.

Adenosine Triphosphate↗
PubMed1997

Postoperative epidural infusion: a randomized, double-blind, dose-finding trial of clonidine in combination with bupivacaine and fentanyl.

The aim of this randomized, double-blind trial of postoperative thoracic epidural analgesic infusions was to determine whether clonidine at 10 microg/h (group C10, n = 22), 15 microg/h (Group C15, n = 24), or 20 microg/h (Group C20, n = 24) improved postoperative analgesia in patients undergoing abdominal gynecologic surgery, without side effects or hemodynamic changes, when added to a 5-mL/h infusion of 0.125% bupivacaine and fentanyl 2 microg/mL (Group CO, n = 22). The 24-h study infusion was supplemented, as required, by patient-controlled epidural fentanyl. Groups were similar for age, weight, duration, and type of surgery. Clonidine produced a dose-dependent improvement in analgesia at rest. Only 20 microg/h significantly increased the percentage of patients who experienced no pain with coughing (relative risk 1.44, 95% confidence interval 1.24-1.94), reduced pain scores with coughing (P < 0.05), and significantly lowered supplementary fentanyl requirements (P < 0.05). Groups were similar for sedation, pruritus, nausea, time to ambulation, and satisfaction with analgesia. Clonidine produced a dose-dependent decrease in blood pressure and pulse rate and an increase in vasopressor requirement (P < 0.01). Epidural clonidine infused at 20 microg/h improves analgesia during coughing when combined with epidural bupivacaine-fentanyl in patients undergoing lower abdominal surgery but is associated with hemodynamic changes and increased vasopressor requirement.

Adrenergic alpha-Agonists↗
PubMed1997

Hippocampal volumetry with magnetic resonance imaging: a cost-effective validated solution.

PURPOSE: The clinical utility of hippocampal volumetry is well documented, but the materials and techniques required to perform the procedure are not widely available outside major research centers. We describe a personal computer-based method of volumetric data analysis. METHODS: Using a 1.0-T scanner, we obtained 2-mm-thick tilted coronal MPRAGE magnetic resonance imaging (MRI) scans of 20 healthy volunteers aged 20-38 years. We used an inexpensive utility program to extract image information and an NIH Image for image analysis. The hippocampal formations were traced with a graphics tablet and landmarks described by Watson et al. (Neurology 1992;42:1743-50). Overlays of individual observers' tracings were used to fine tune the selection of landmarks and boundaries. Filled-in silhouette pairs generated from these "training tracings" were compared to determine how well observers could visually quantify area differences. RESULTS: Visual detection of asymmetry of silhouette pairs was sensitive, but the magnitude of asymmetry was underestimated. We achieved intraobserver coefficients of variation of right/left volume ratios between 0.82 and 3.16 and an interobserver range of volume ratios of 6%. In 20 healthy controls aged 20-38 years, the mean right and left hippocampal volumes were 2,911 mm3 and 2,836 mm3, respectively. The lower limits of normal were 2,217 mm3 for the right and 2,178 mm3 for the left. The mean right/left hippocampal ratio was 1.03, and the limits of normal (3 SD) for this were 0.95 to 1.10. CONCLUSIONS: Hippocampal volumetry can be performed reliably and economically. Our methodology makes it possible for different observers to generate consistent and comparable measurements.

Adult↗