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Biomedical subjects

W Wong

Publications and source records attributed to W Wong.

At least 91 records · Page 5Linked to original sources
PubMed1997

N-Type calcium channels in the developing rat hippocampus: subunit, complex, and regional expression.

The expression of multiple classes of voltage-dependent calcium channels (VDCCs) allows neurons to tailor calcium signaling to functionally discrete cellular regions. In the developing hippocampus a central issue is whether the expression of VDCC subtypes plays a role in key phases such as migration and synaptogenesis. Using radioligand binding and immunoblotting, we show that some N-type VDCCs exist before birth, consistent with a role in migration; however, most N-VDCC subunit expression is postnatal, coinciding with synaptogenesis. Immunoprecipitation studies indicate that the increased expression of N-VDCCs in early development occurs without subunit switching because there is no change in the fraction of beta3 subunits in the N-VDCC alpha1B-beta3 heteromers. Fluorescence imaging of cell surface N-VDCCs during this period reveals that N-VDCCs are expressed on somata before dendrites and that this expression is asynchronous between different subfields of the hippocampus (CA3-CA4 before CA1-CA2 and dentate gyrus). Our data argue that N-VDCC expression is an important cue in the genesis of synaptic transmission in discrete hippocampal subfields.

Animals↗
PubMed1997

Renal transplantation in children; the Auckland experience 1980-96.

AIM: To review the experience and outcome of renal transplantation in children who received a renal allograft at the Auckland Children's Hospital between January 1980 and June 1996. METHODS: Retrospective review of patient records and access to data collected through the ANZDATA Registry. Forty one renal transplants were undertaken in 39 children. Prednisone and Azathioprine were the mainstay of the immunosuppressive regimen from 1980 to 1985, then cyclosporin A was introduced in 1986. Median age of first graft was 11 years (range 1.6-14 years). There were 34 living related and 7 cadaveric grafts and 17 males and 22 females. Thirteen children (33%) had a primary glomerular disorder as the cause of renal failure. Another 9 (28%) had reflux nephropathy and a further 8 (18%) had congenital renal dysplasia/hypoplasia either as primary cause or secondary to lower urinary obstruction. RESULTS: Survival analysis showed that 93% of grafts were functioning at 12 months and 73% were still functioning at 5 years. Longest surviving transplant is 16 years. Ten primary grafts were lost with the most common cause being chronic rejection, accounting for 50% of all transplants lost. Recurrence of primary disease was the second most common (4 of 13) cause of graft failure. There was one malignancy in this series with a child developing a Kaposi's sarcoma. CONCLUSIONS: Renal transplantation is a successful treatment of endstage renal failure in children. Chronic rejection remains a major cause of graft loss and better immunosuppressive strategies are required to deal with this problem.

Adolescent↗
PubMed1997

Pretransplant administration of a single donor class I major histocompatibility complex molecule is sufficient for the indefinite survival of fully allogeneic cardiac allografts: evidence for linked epitope suppression.

BACKGROUND: Allograft survival can be prolonged by the administration of alloantigen(s) before transplantation. Blood transfusion is the commonest form of alloantigen pretreatment currently used in clinical practice. However, for recipients of organs from cadaver donors, it is not possible to predict the identity of the organ donor in advance. Therefore, it is highly unlikely that all the alloantigens expressed by a cadaver organ donor will be represented in the alloantigen pretreatment inoculum. We have previously shown that it is not necessary to expose the recipient to the full complement of donor alloantigens to induce long-term survival of a subsequent cardiac allograft. Here, we investigated the in vivo mechanism responsible for this phenomena. METHODS: Unresponsiveness to the mouse MHC class I molecule Kb was induced in CBA.Ca (H2k) recipients by administration of bone marrow cells from transgenic CBA mice, CBK (H2k + Kb) before transplantation of fully allogeneic and F1 vascularized cardiac allografts. RESULTS: Pretreatment with CBK bone marrow cells resulted in the long-term survival of all cardiac allografts expressing H2-Kb. For example, C57BL/10 (H2b) and (CBKxBALB/c) F1 (H2k,d + Kb) cardiac allografts were accepted by recipients treated with CBK bone marrow cells before transplantation. In contrast, allografts that did not express Kb, such as BALB/c (H2d) or (CBAxBALB/c) F1 (H2k,d), were rejected acutely, with a median survival time (MST) of 7 and 6 days, respectively, in recipients treated with CBK bone marrow cells. Furthermore, when recipients pretreated with CBK bone marrow cells were grafted with a BALB/c heart and a CBK heart simultaneously, the BALB/c hearts were rejected (MST=10 days), whereas the CBK hearts were accepted. By contrast, in the maintenance phase (i.e., after transplantation), recipients with long-term surviving (CBKxBALB/c) F1 hearts (> 100 days) were found to accept BALB/c hearts indefinitely, whereas fourth-party B10.S (H2s) grafts were rejected (MST=7.5 days). This indicated that the allografts bearing Kb could tolerize recipients to other alloantigens expressed by the transplanted heart. CONCLUSIONS: These data provide clear evidence for linked epitope suppression in the induction of operational tolerance in vivo.

Animals↗
PubMed1997

Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production.

Interferon-gamma-inducing factor (IGIF, interleukin-18) is a recently described cytokine that shares structural features with the interleukin-1 (IL-1) family of proteins and functional properties with IL-12. Like IL-12, IGIF is a potent inducer of interferon (IFN)-gamma from T cells and natural killer cells. IGIF is synthesized as a biologically inactive precursor molecule (proIGIF). The cellular production of IL-1beta, a cytokine implicated in a variety of inflammatory diseases, requires cleavage of its precursor (proIL-1beta) at an Asp-X site by interleukin-1beta-converting enzyme (ICE, recently termed caspase-1). The Asp-X sequence at the putative processing site in proIGIF suggests that a protease such as caspase-1 might be involved in the maturation of IGIF. Here we demonstrate that caspase-1 processes proIGIF and proIL-1beta with equivalent efficiencies in vitro. A selective caspase-1 inhibitor blocks both lipopolysaccharide-induced IL-1beta and IFN-gamma production from human mononuclear cells. Furthermore, caspase-1-deficient mice are defective in lipopolysaccharide-induced IFN-gamma production. Our results thus implicate caspase-1 in the physiological production of IGIF and demonstrate that it plays a critical role in the regulation of multiple proinflammatory cytokines. Specific caspase-1 inhibitors would provide a new class of anti-inflammatory drugs with multipotent action.

Animals↗
PubMed1997

Lower gastrointestinal tract perforation in preterm infants treated with dexamethasone for bronchopulmonary dysplasia

Two cases of ileal perforation in preterm infants treated with high-dose dexamethasone for bronchopulmonary dysplasia are described. Corticosteroid-induced gastroduodenal haemorrhage or perforation has been well documented, but less known to most clinicians is that the lower gastrointestinal tract can also be involved. Unlike previous reported cases in which affected infants deteriorated rapidly and became moribund within hours of onset of symptoms, "silent" perforations detected on routine radiograph or escaping clinical recognition until at an advanced stage can be the initial presentation. The need for greater vigilance and a low threshold for abdominal investigations are emphasised in preterm infants treated with dexamethasone.

Journal Article↗
PubMed1997

Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution.

Heparin-induced thrombocytopenia with thrombosis (HITT) can lead to serious morbidity and may be potentially fatal. We reviewed our experience with this entity over a 4-year period, to determine the following: 1) incidence and type of thrombosis in patients with heparin-induced thrombocytopenia (HIT), 2) clinical consequences of thrombosis, i.e., amputation, cerebrovascular accidents and death, 3) risk factors associated with development of thrombosis, and 4) impact of therapy on clinical outcomes in patients with HITT. Between 1991-1994, 108 patients were diagnosed to have HIT by heparin-induced platelet aggregation test. Thirty-two (29%) of these developed thrombotic complications, of which 20 were venous, 8 arterial, and 4 both. Five of the 32 died, 3 underwent amputations, and 3 had cerebrovascular accidents. The patients who developed thrombotic complications, when compared to those with HIT alone, were older (68.7 +/- 11.5 vs. 63.3 +/- 16 years, P = .05), had more severe thrombocytopenia (platelet count 46,300 +/- 30,400/mm3 vs. 62,500 +/- 34,400/mm3, P = .02), and developed it earlier (6.0 +/- 2.9 vs. 7.4 +/- 3.1 days, P = .03). Multivariate analysis showed that severity of thrombocytopenia and early fall in platelet count were independent risk factors for development of thrombotic complications. We did not find an association between development of thrombosis and clinical events (myocardial infarction, cardiac procedures or surgery, noncardiac surgery, and sepsis) that occurred immediately prior to onset of thrombocytopenia. Heparin was stopped in all 32 patients with HITT. Six received no additional therapy, and one received a single dose of aspirin. Three of these 7 died. The other 25 received anticoagulant or multiagent therapy, with 2 deaths. The death rate was lower in those who were treated with anticoagulant or multiagent therapy (P = .05). We conclude that: 1) Thrombotic complications occur in about 29% of hospitalized patients who develop HIT. 2) Early, severe fall in platelet count in elderly patients receiving heparin appears to be associated with development of thrombotic complications. 3) Our data do not show an association between development of thrombotic complications and clinical events immediately preceding the diagnosis of HIT. 4) In addition to discontinuation of heparin, anticoagulant or thrombolytic therapy should be considered in patients with HITT.

Anticoagulants↗
PubMed1997

Aerosol delivery to non-ventilated infants by metered dose inhaler: should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 micrograms/dose) of MDI albuterol through a neonatal Aerochamber 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber: 51.2 +/- 3.1% vs. 35.0 +/- 2.8%, P < 0.0001; Babyhaler: 38.8 +/- 2.3% vs. 19.2 +/- 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used.

Aerosols↗
PubMed1997

Evidence of enhanced type 2 immune response and impaired upregulation of a type 1 response in frail elderly nursing home residents.

Peripheral blood mononuclear cells (PBMC) of frail elderly nursing home residents had significantly higher PHA-induced interleukin-10 (IL-10) production compared to PBMC's from young control subjects. No correlation was observed between IL-10 production and interleukin-12 (IL-12) p40 production, proliferative response or with the proportion of CD28-negative T cells. To better characterize the host response to a ubiquitous pathogen, the dose response and time-dependent (kinetic) production of IL-10 and IL-12 p40 of PBMC stimulated with Staphylococcus aureus Cowan (SAC) was studied. IL-10 production continued to increase at 48 h, while IL-12 p40 levels declined or remained stable, in both young and elderly subjects. In analyzing how excessive IL-10 production might influence antigen presenting cell functions, IL-12 was markedly inhibited by recombinant IL-10 (rIL-10), while anti-IL-10 enhances IL-12 p40 production in cultures from young controls; but the PBMC cultured from an elderly cohort were not able to generate similar absolute levels of IL-12 p40 even in the presence of anti-IL-10. These preliminary data suggest that there may be both over production of IL-10 in some individuals, as well an an impaired ability to upregulate a T Helper 1 (type 1) reaction. These age-related changes could even be more dramatic at the tissue level and contribute to the impaired delayed type hypersensitivity (DTH) and failed host defense to infection, such as to primary and reactivation tuberculosis.

Aged↗
PubMed1997

Simulation of human sensory performance.

The capacity of human sensory systems for transmitting information has been approximated in the past by using statistical estimators. However, a substantial margin of error remained. The problem is that the error can be reduced to a negligible level only by increasing the number of human trials or tests to the order of about 10(4). Since a human subject can perform at peak only in the order of 10(2) trials per day, the requisite total number of trials could be obtained realistically only by pooling of data from several subjects. Following Houtsma, we have overcome this problem to a large extent by the use of computer simulation. By introducing parameters characteristic of a given subject into the simulation program, we are able to reproduce the subject's performance (say for 500 trials), and to extrapolate his or her performance using the simulation program to 30000 trials. In this way we can establish limits to the capacity of a single human being to transmit information.

Auditory Pathways↗
PubMed1997

The role of retrograde urethrography in the planning of prostate cancer radiotherapy.

This analysis was performed to examine the role of retrograde urethrography in the planning of prostate cancer irradiation. Retrograde urethrograms were performed in 91 patients at the time of simulation. The abrupt narrowing of the contrast column in the urethra was visualized in each case. The distance between the abrupt narrowing of the contrast column and a line connecting the lower poles of the ischial tuberosities was measured in each patient. This distance ranged from 2 to 33 mm with a mean and median of 14 mm. A review of the literature revealed that the abrupt narrowing of the contrast column lies between 5-13 mm inferior to the prostate apex as determined by computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography. The prostate apex will be adequately covered by placing the inferior edge of the treatment field 15 mm below the abrupt narrowing of the contrast column. This technique will result in at least 20 mm between the prostate apex and the inferior field edge. Performing a retrograde urethrogram at the time of simulation can help prevent geographic misses of the prostate gland when delivering radiation for prostate cancer.

Aged↗
PubMed1997

Differences in lipoprotein lipid concentration and composition modify the plasma distribution of cyclosporine.

PURPOSE: The purpose of this study was to define the relationship between lipoprotein (LP) lipid concentration and composition and the distribution of cyclosporine (CSA) in human plasma. METHODS: 3H-CSA LP distribution was determined in normolipidemic human plasma that had been separated into different LP and lipoprotein-deficient plasma (LPDP) fractions by either affinity chromatography coupled with ultracentrifugation, density gradient ultracentrifugation or fast protein liquid chromatography. 3H-CSA LP distribution (at a concentration of 1000 ng/ml) was also determined in patient plasma samples with defined dyslipidemias. Furthermore, 3H-CSA LP distribution was determined in patient plasma samples of varying LP lipid concentrations. Following incubation, the plasma samples were separated into their LP and LPDP fractions by sequential phosphotungistic acid precipitation in the dyslipidemia studies and by density gradient ultracentrifugation in the specific lipid profile studies and assayed for CSA by radioactivity. Total plasma and lipoprotein cholesterol (TC), triglyceride (TG) and protein (TP) concentrations in each sample were determined by enzymatic assays. RESULTS: When the LP distribution of CSA was determined using three different LP separation techniques, the percent of CSA recovered in the LP-rich fraction was greater than 90% and the LP binding profiles were similar with most of the drug bound to plasma high-density (HDL) and low-density (LDL) lipoproteins. When 3H-CSA was incubated in dyslipidemic human plasma or specific patient plasma of varying LP lipid concentrations the following relationships were observed. As the very low-density (VLDL) and LDL cholesterol and triglyceride concentrations increased, the percent of CSA recovered within the VLDL and LDL fractions increased. The percent of CSA recovered within the HDL fraction significantly decreased as HDL triglyceride concentrations increased. The percent of CSA recovered in the LPDP fraction remained constant except in hypercholesterolemic/hypertriglyceridemic plasma where the percent of CSA recovered decreased. Furthermore, increases in VLDL and HDL TG/TC ratio resulted in a greater percentage of CSA recovered in VLDL but less in HDL. CONCLUSIONS: These findings suggest that changes in the total and plasma LP lipid concentration and composition influence the LP binding of CSA and may explain differences in the pharmacological activity and toxicity of CSA when administered to patients with different lipid profiles.

Centrifugation, Density Gradient↗
PubMed1997

Eye protection for newborns under phototherapy: comparison between a modified headbox and the conventional eyepatches.

In a randomized trial comparing a modified oxygen headbox with conventional eye patches for protecting the eyes of newborn infants undergoing phototherapy, the use of the headbox did not interfere with phototherapy treatment and was preferred by the nursing staff, as shown by an opinion survey. This, plus our previously reported finding that the headbox was associated with less eye infection, less periorbital skin irritation and less accidental exposure of the eyes due to displacement of the protective devices, suggests that the headbox provides a convenient and inexpensive alternative method of eye protection. The device may be particularly useful in busy and under-staffed neonatal units where vigilant eye care of infants undergoing phototherapy may be difficult.

Attitude of Health Personnel↗
PubMed1997

Erythromycin treatment for gastrointestinal dysmotility in preterm infants.

OBJECTIVE: To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants. METHODOLOGY: A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre. RESULTS: All responded favourably without adverse effects and tolerated full enteral feeding within 1-2 weeks of the commencement of the drug. CONCLUSIONS: As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.

Erythromycin↗
PubMed1997

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants.

OBJECTIVES: A prospective study comparing the efficacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (< 1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus. METHODOLOGY: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (+/-1 week) and birthweight (+/-100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group. RESULTS: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment (P > 0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups (P < 0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group. CONCLUSIONS: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.

Administration, Oral↗
PubMed1997

Central diabetes insipidus in a newborn with deletion of chromosome 7q.

We report an infant with midline craniofacial defects and holoprosencephaly due to chromosome 46, XY, del (7) (pter-->q34) who presented at 1 week of age with central diabetes insipidus. The importance of hypothalamic-pituitary endocrine investigation in patients with this syndrome, and more generally, in patients with midline craniofacial malformation or holoprosencephaly is emphasized. As infants with chromosome 7q deletion bear close phenotypic resemblance to infants of Trisomy 13, chromosomal confirmation and karyotype banding is mandatory to establish an accurate diagnosis and for genetic counselling of their parents.

Abnormalities, Multiple↗
PubMed1997

Vascular air embolism: a rare complication of nasal CPAP.

A preterm infant developed bilateral tension pneumothoraces and extensive vascular air embolism 6 h after being commenced on nasal continuous positive airway pressure (CPAP). Neonatal clinicians should be aware that catastrophic vascular air embolism could occur in infants receiving nasal CPAP, a modality of respiratory support conventionally considered non-invasive and 'safe'.

Embolism, Air↗
PubMed1997

High frequency oscillatory ventilation in infants with increased intra-abdominal pressure.

AIMS: To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated. METHODS: Eight infants (25 to 38 gestational weeks, birthweight 600-3200 g, postnatal age 1 to 190 days) with a variety of intra-abdominal pathologies, resulting in severe abdominal distension and failure of conventional ventilation, were studied. RESULTS: The oxygenation status of all infants significantly improved within an hour of changing from conventional to high frequency oscillatory ventilation. Infants who were hypercapneic on conventional ventilation also showed a reduction in PaCO2. As a group, the mean (SD) PaO2/FIO2 improved from 4.99 (0.98) kpa to 11.55 (3.8) kpa (P = 0.002), and the PaCO2 from 6.48 (2.12) kpa to 4.89 (1.22) kpa (P = 0.028). These improvements were sustained throughout the next 48 hours. CONCLUSION: High frequency oscillatory ventilation seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure.

Abdomen↗