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Biomedical subjects

W Wong

Publications and source records attributed to W Wong.

At least 109 records · Page 6Linked to original sources
PubMed1997

Randomised controlled trial: comparison of colloid or crystalloid for partial exchange transfusion for treatment of neonatal polycythaemia.

AIM: To compare the efficacy of using isotonic saline (crystalloid) or 5% albumin (colloid) as replacement fluid in partial exchange transfusion (PET) for the treatment of neonatal polycythaemia. METHODS: One hundred and two polycythaemic full term infants were randomly allocated to receive PET with either isotonic saline or 5% albumin. The criteria for PET were: (a) venous haematocrit > or = 0.7; or (b) venous haematocrit 0.65-0.69 with symptoms or signs attributable to polycythaemia. RESULTS: PET with either saline (n = 53) or 5% albumin (n = 50) resulted in a significant and sustained decline in haematocrit up to 24 hours after PET. Although the immediate haemodilution effect of isotonic saline was statistically smaller than that of 5% albumin (decline in haematocrit 19.3% vs 22.8% of pre-PET value), the difference was too small to be of any clinical significance, and the haematocrit at 4 or 24 hours after PET did not differ significantly between the two groups. PET with either replacement fluid was not associated with any complication. The serum sodium and potassium concentrations were not significantly affected by the PET in either group. CONCLUSIONS: Both isotonic saline and 5% albumin are effective when used as replacement fluid in PET for the treatment of neonatal polycythaemia. Isotonic saline, which is cheaper and free of infection, should be the replacement fluid of choice.

Albumins↗
PubMed1997

Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants.

AIMS: To evaluate the commonly used markers--namely IL-6, TNF alpha, IL-1 beta, C-reactive protein and E-selection for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment. METHODS: Very low birthweight infants in whom clinical sepsis was suspected when they were > 72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined. RESULTS: One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNF alpha 17 pg/ml, IL-1 beta 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNF alpha on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection. CONCLUSIONS: Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNF alpha should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.

Biomarkers↗
PubMed1997

Pituitary-adrenal response in preterm very low birth weight infants after treatment with antenatal corticosteroids.

Antenatal corticosteroids have been widely used for the prevention of respiratory distress syndrome in preterm neonates, yet little is known about their effects on the hypothalamic-pituitary-adrenal axis in these infants. We prospectively evaluated pituitary-adrenal function in 61 preterm (< 32 gestational weeks), very low birth weight (< 1500 g) infants on days 7 and 14 of life using the human CRH stimulation test. The baseline and poststimulation plasma ACTH and serum cortisol concentrations did not differ significantly between infants whose mothers received no antenatal corticosteroids, and those whose mothers received 1-2 doses or > 2 doses (mean 7.2 doses) of prenatal dexamethasone (P = > 0.12). The number of doses of dexamethasone and the time intervals between the last dose of drug and delivery did not significantly affect the pituitary-adrenal responsiveness on days 7 and 14 of life. Among infants who did not require mechanical ventilation at the time of the human CRH test, significantly higher plasma ACTH (P < 0.014) and lower serum cortisol concentrations (P < 0.02) were found on day 14 than on day 7. In contrast, none of the poststimulation hormone concentrations were significantly different in ventilated infants between days 7 and 14. The relationship between the blood hormone concentrations in each time epoch (day 7 and day 14) and possible confounding factors including gestational and postconceptional age, birth weight, sex, Apgar scores, mode of delivery, single or higher order births, and mode of ventilation were determined. Plasma ACTH concentrations on day 7 were found to be significantly higher in ventilated than in nonventilated infants (P = 0.006). However, none of the aforementioned factors correlated significantly with plasma ACTH concentrations on day 14. Serum cortisol concentrations on day 7 were significantly higher in infants of greater gestational age (P = 0.039) and birth weight (P = 0.013), with lower Apgar scores at 1 and 5 min (P = 0.021 and P = 0.049, respectively), and in those delivered vaginally (P = 0.047). Similarly, serum cortisol concentrations on day 14 were found to be significantly higher in infants with lower Apgar scores at 1 and 5 min (P = 0.011 and P = 0.014, respectively) and in infants requiring mechanical ventilation (P = 0.014). Our results suggest that single or multiple courses of antenatal dexamethasone have no long-lasting suppressive effects on pituitary-adrenal function in preterm, very low birth weight infants. Maturation of pituitary function appears to be more advanced than adrenal function. The organ's ability to respond appropriately to various stressful stimuli indicates that the pituitary-adrenal axis is highly responsive at these early gestational ages.

Adrenal Cortex Hormones↗
PubMed1997

The pituitary-adrenal responses to exogenous human corticotropin-releasing hormone in preterm, very low birth weight infants.

To evaluate the pituitary-adrenal reserve and to standardize the methodology of performing the human CRH (hCRH) stimulation test, we performed the hCRH test on 14 preterm (< 32 gestational weeks), very low birth weight infants, who did not receive antenatal or postnatal corticosteroid treatment, on days 7 and 14 of life. Blood samples were obtained 0 (baseline), 15, 30, and 60 min after an iv dose of hCRH (1 microgram/kg). The plasma ACTH concentration rose from a basal value of 5.7 +/- 0.6 pmol/L (mean +/- SEM) to 11.9 +/- 2.1 pmol/L (P < 0.005), 9.2 +/- 1.2 pmol/L (P < 0.005), and 7.7 +/- 0.8 pmol/L (P < 0.005) at 15, 30, and 60 min, respectively. The corresponding rises in serum cortisol from a basal concentration of 396 +/- 67 nmol/L were 509 +/- 71 nmol/L (P < 0.0001), 647 +/- 62 nmol/L (P < 0.0001), and 578 +/- 60 nmol/L (P < 0.0001). The plasma ACTH concentration consistently peaked early at 15 min, whereas the maximum cortisol response occurred 30 min post-hCRH stimulation. No significant differences were detected between the hCRH tests performed on days 7 and 14 (P > 0.15). Mechanical ventilation, infant gender, and mode of delivery did not significantly influence the hormonal responses (P > 0.25). We have defined in this study the pattern, the magnitude of the pituitary-adrenal response, and the timing of the peak concentrations of plasma ACTH and serum cortisol in relation to a standard iv dose of hCRH. The hCRH test in very low birth weight infants appears to be safe and reproducible, and produces a pituitary-adrenal response comparable to that seen in older children and adults, indicating that pituitary-adrenal function is mature at these early stages of gestation.

Adrenocorticotropic Hormone↗
PubMed1997

Pituitary-adrenal suppression and recovery in preterm very low birth weight infants after dexamethasone treatment for bronchopulmonary dysplasia.

High dose dexamethasone is frequently used for the treatment of neonatal respiratory conditions and to facilitate weaning from mechanical ventilation in preterm, very low birth weight infants. However, very little is known about the severity, site, and duration of steroid-induced hypothalamic-pituitary-adrenal axis suppression in this category of patients. Twenty-three preterm, very low birth weight infants who received a full 3-week dose-tapering course of dexamethasone were prospectively studied, with a human CRH stimulation test performed at three different times: before the start of steroid treatment (week 0), immediately after the course (week 3), and 4 weeks after stopping dexamethasone (week 7). Plasma ACTH and serum cortisol concentrations were measured at 0 (baseline), 15, 30, and 60 min. Immediately after the steroid course (week 3), both basal and poststimulation plasma ACTH and serum cortisol concentrations were markedly suppressed. The hormone concentrations at 0, 15, 30, and 60 min in week 3 were significantly lower than their corresponding levels in week 0 (P < 0.0001 for both ACTH and cortisol) and week 7 (P < 0.0001 and P < 0.005 for ACTH and cortisol, respectively). In contrast, when the hormone levels in week 7 were compared to their corresponding concentrations in week 0, only the 60 min serum cortisol concentration in week 7 was significantly lower (P = 0.02). The currently used dosage of dexamethasone caused severe pituitary-adrenal suppression immediately after treatment, but substantial recovery of the endocrine axis was observed 4 weeks after discontinuation of therapy. Although the recovery appeared to be earlier with the pituitary center, both pituitary and adrenal glands were capable of mounting a biochemically adequate response to exogenous human CRH stimulation at this stage. Steroid replacement therapy may be desirable at a time of stress in the immediate posttreatment period, but it would seem unnecessary 1 month after stopping dexamethasone treatment.

Adrenal Gland Diseases↗
PubMed1997

Unification of psychophysical phenomena: the complete form of Fechner's law.

Many of the laws and empirical observations of fundamental psychophysics can be unified with a single equation, which has been called the complete form of Fechner's law. It can be shown that this law embraces both of the commonly used forms: Stevens's and Fechner's laws. It assumes one or the other form with appropriate values of the parameters. However, the complete equation confers an advantage beyond simply containing the classical laws. It offers greater flexibility in the representation of experimental data. It is shown that psychophysical phenomena may be represented by any number of triplets of quantities: subjective magnitude of stimulus, subjective just noticeable difference (jnd), and differential threshold. Each of the preceding quantities are functions of the physical magnitude of the stimulus. The investigator has the license to choose two of these quantities in the form he or she thinks is best; the third quantity is determined by the choice of the first two. Thus, for example, different forms of the law of sensation and different forms of the mathematical function for differential threshold may coexist with equal validity.

Auditory Threshold↗
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.

Anti-Inflammatory Agents↗
PubMed1996

Acute renal failure in the paediatric intensive care unit.

AIMS: To review a group of children with acute renal failure (ARF) requiring renal replacement therapy in a paediatric intensive care unit (PICU). METHODS: Case records of children admitted to paediatric intensive care unit between January 1992 and July 1995 were reviewed for demography, diagnosis, modality of treatment, duration, complications of therapy and renal outcome. Long term follow up was sought from patients' referring paediatricians. RESULTS: Twenty children with a mean age of 2 years and 3 months required acute renal replacement therapy. The most common cause was diarrhoea associated haemolytic uraemic syndrome with a mean duration of dialysis of 11.5 (SD 3.1) days (range 5-15. Four children had septicaemic illnesses; three with multiorgan system failure, one of whom died. Peritoneal dialysis was the only modality in 16 patients and four children were treated with continuous venovenous haemofiltration. Eight of the 20 patients were discharged from the paediatric intensive care unit with normal renal function as judged by serum creatinine. Long-term follow up showed normalisation of serum creatinine in a further eight of ten patients. CONCLUSIONS: The most common cause of acute renal failure was diarrhoea associated haemolytic uraemic syndrome with an excellent outcome (100% patient survival). Children who had acute renal failure due to other illnesses had a higher mortality (27%).

Acute Disease↗
PubMed1996

Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis.

Recent studies have shown that protein kinase C (PKC) delta is proteolytically activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. However, the relationship of PKC delta cleavage to induction of apoptosis is unknown. The present studies demonstrate that full-length PKC delta is cleaved at DMQD330N to a catalytically active fragment by the cysteine protease CPP32. The results also demonstrate that overexpression of the catalytic kinase fragment in cells is associated with chromatin condensation, nuclear fragmentation, induction of sub-G1 phase DNA and lethality. By contrast, overexpression of full-length PKC delta or a kinase inactive PKC delta fragment had no detectable effect. The findings suggest that proteolytic activation of PKC delta by a CPP32-like protease contributes to phenotypic changes associated with apoptosis.

Amino Acid Sequence↗
PubMed1996

Syngeneic bone marrow expressing a single donor class I MHC molecule permits acceptance of a fully allogeneic cardiac allograft.

Bone marrow cells may be a useful vehicle for pretransplant delivery of alloantigen to induce tolerance in vivo. However, infusion of fully allogeneic bone marrow cells carries the risk of graft-versus-host disease. In order to reduce this risk while retaining the tolerogenic potential of the bone marrow infusion, we have investigated the ability of recipient bone marrow cells expressing a single donor MHC class I antigen to induce specific unresponsiveness in vivo. We show that 5x10(7) and 5x10(6) bone marrow cells from a transgenic strain of CBA mice, CBK, that express a single donor class I MHC gene, H2Kb (H2k + H2Kb), were able to induce long term survival of a fully allogeneic C57BL/10 (H2b) cardiac allograft in 80% and 20% of unmanipulated CBA (H2k) recipients, respectively, when administered intravenousely on the day of transplantation. In contrast, the same doses of fully allogeneic C57BL/10 donor bone marrow were completely ineffective at prolonging graft survival. When the interval between bone marrow infusion and transplantation was increased to 14 days, CBK bone marrow at either dose (5x10(6) and 5x10(7)) induced long term survival of C57BL/10 cardiac allografts in all recipients (MST>100 days) while fully allogeneic donor bone marrow was ineffective (MST=7, 5x10(6) cells; MST=6, 5x10(7)). Only when 27 or 42 days had elapsed between bone marrow infusion and transplantation did fully allogeneic bone marrow exert a beneficial effect on graft survival. Administration of 5x10(6) C57BL/10 bone marrow cells 27 and 42 days before transplantation resulted in long term survival of C57BL/10 hearts in 67% and 75% of CBA recipients. Next, we investigated whether manipulating the periphery of the recipient with a depleting anti-Cd4(4) monoclonal antibody before bone marrow infusion would facilitate the induction of unresponsiveness. When pretreatment with bone marrow cells was combined with anti-Cd4 monoclonal antibody 28 days before transplantation, a 10-fold reduction in the number of either C57BL/10 or CBK bone marrow cells required to induce tolerance was observed. These data confirm that bone marrow is a suitable vehicle for alloantigen delivery at the time of, or before, transplantation, on its own or in combination with anti-Cd4. The use of recipient type bone marrow cells expressing one or more donor MHC genes may be more effective than fully allogeneic, donor bone marrow cells in inducing tolerance in vivo. This difference may have important clinical implications for the current trials of donor bone marrow given at the time of transplantation in order to augment chimerism and to prolong graft survival.

Animals↗
PubMed1996

Transplant renal artery stenosis in 77 patients--does it have an immunological cause?

Transplant renal artery stenosis (TRAS) is a common complication after transplantation and is an important cause of graft dysfunction. Damage from graft rejection, trauma, and atherosclerosis have been implicated as possible causes. We reviewed all 917 patients transplanted in our unit since 1978 to study the prevalence, clinical features, and possible causes of TRAS. Seventy-seven patients with TRAS were identified. The detected incidence was 2.4% before the introduction of color doppler ultrasonography (CDU) and rose to 12.4% after CDU was introduced in 1985, giving an overall incidence of 8.4% during a mean follow-up period of 6.9 years. The TRAS group was compared with a control group of 77 transplanted patients matched for age, year of transplant, sex, and number of previous grafts. Mean ages for the study and control groups were 43.6 +/- 15 and 44.8 +/- 13.7 yr. A total of 25% of cases of TRAS were diagnosed within the first 8 wk of transplantation and in 60% within the first 30 wk (median = 23 wk). All patients were treated with angioplasty, 28 patients had recurrence of TRAS requiring multiple angioplasties (maximum 5) and 1 went on to have surgery. Angioplasty resulted in a significant fall in plasma creatinine. Patient and graft survival were significantly worse in the TRAS group: 69% vs. 83% (P < 0.05) and 56% vs. 74% (P < 0.05) (TRAS vs. Control), respectively. There was a significantly higher incidence of rejection, especially cellular rejection in the TRAS group, 0.67 vs. 0.35 episodes per patient (P < 0.01) (TRAS vs. Control). Recurrence but not occurrence of TRAS was associated with the use of cyclosporine.

Adult↗
PubMed1996

Tophaceous pseudogout.

We present an unusual case of tophaceous pseudogout in the atlantoaxial joint with progressive cervical cord compression symptoms and lack of additional clinical manifestations of CPPD crystal deposition disease. This represents only the fourth reported case in the medical literature.

Aged↗
PubMed1996

A case of neonatal Bartter's syndrome.

We describe a child with a neonatal presentation of Bartter's syndrome. Unlike infants previously described with a similar clinical presentation, the urinary excretion rate of prostaglandin E2 in this child was similar to normal children and Tamm-Horsfall protein was distributed normally in the thick ascending limb of the loop of Henle. The child failed to respond to indomethacin alone, but thrived after the addition of the angiotensin converting enzyme inhibitor, captopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Design and synthesis of C-linked fucosides as inhibitors of E-selectin.

Two series of C-linked fucosides as mimetics for the tetrasaccharide sialyl Lewis X have been synthesized and tested as inhibitors of E-Selectin. The fucopeptides have been prepared from three key intermediates, including alpha-C-allyl fucose, natural and unnatural amino acids bearing hydroxyl groups and an alpha, omega-diacid moiety for the imitation of the essential three parts of SLex, i.e., the Fuc, Gal, and NeuAc. The nature and distance of the linkage of the fucose moiety to the amino acids as well as the distance between the amino acids and the terminal carboxylic acid group turned out to be crucial for the biological activity. In addition the necessity of both OH groups (4- and 6-OH) in the Gal part could be confirmed. Conformational NMR study of the most active mimetic supports the structure-activity relationship. A second series of mimetics was prepared, where Fuc and Gal moieties were purely C-linked. In the synthesis of beta-C-allyl galactose an intramolecular 1,2-hydride shift led to an interesting side product. However, the substituted glycosidic oxygens led to a substantial loss of conformational constrain, which could not be compensated and resulted in low activity.

E-Selectin↗
PubMed1996

Varicella exposure in a neonatal intensive care unit: emergency management and control measures.

We describe an exposure of varicella zoster virus in our neonatal intensive-care unit and the emergency procedures instituted to prevent an outbreak. Fifty-seven infants and 129 staff members were exposed but none developed chickenpox. The measures included rapid identification of varicella antibody status in all neonates and those staff members with uncertain history of varicella infection; cohorting of exposed infants according to immune status; and prompt administration of varicella zoster immunoglobulin to susceptible patients. The recommendation of the American Academy of Pediatrics did not accurately predict the immune status of preterm infants, as only one of the eight susceptible infants would have qualified for immunoglobulin prophylaxis if their guidelines had been followed. Mass screening of all exposed infants using the varicella zoster enzyme linked immunosorbent assay (ELISA) test was the only reliable means of determining the immune status. Of the four risk factors evaluated for the prediction of antibody status: gestational age, postnatal age, birthweight and episodes of blood transfusion, only postnatal age was found to independently predict the immune status of our patients. Because varicella zoster susceptible staff members are difficult to identify on the basis of history, we suggest that prospective screening of staff in high-risk units be undertaken and vaccination with live varicella vaccine be offered to susceptibles.

Antibodies, Viral↗
PubMed1996

Binding and internalization of the melanocyte stimulating hormone receptor ligand [Nle4, D-Phe7] alpha-MSH in B16 melanoma cells.

The current study aims to ascertain the fate of the melanocyte stimulating hormone (MSH) receptor and its ligand [Nle4, D-Phe7] alpha-MSH (NDP-MSH) following binding to murine B16 melanoma cells. Cells were incubated with [125I]-NDP-MSH for up to 180 min and binding, internalization and degradation determined. Intracellular trafficking of the radiolabel was assessed using Percoll density gradient centrifugation of homogenized cells. Receptor down-regulation and receptor mRNA levels were also measured over 96 hr after exposure to 1 microM ligand. NDP-MSH accumulation increased with time in a temperature-dependent manner and was inhibited by excess peptide. The ligand was rapidly internalized and translocated to the lysosomal compartment where it was degraded. Internalization was accompanied by a loss or down-regulation of cell surface receptors, suggesting internalization of the NDP-MSH-receptor complex. No recycling of the receptors between the plasma membrane and intracellular compartments could be detected in this cell-line. Approximately 15% of the surface receptors were resistant to down-regulation, possibly indicating receptor heterogeneity. Down-regulation persisted for up to 96 hr and was accompanied by a decrease in MSH receptor mRNA levels 48 hr after treatment. However, before this time, transcript levels were the same in treated and control cells. In contrast to what was seen with NDP-MSH, cell surface receptors removed with trypsin were rapidly replaced. These results show that NDP-MSH not only induced MSH receptor internalization but also inhibited receptor turnover, resulting in a prolonged down-regulation. It is concluded that, in B16 cells, the MSH receptor undergoes ligand-dependent internalization, resulting in a prolonged down-regulation.

Animals↗