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Biomedical subjects

K Lui

Publications and source records attributed to K Lui.

At least 37 records · Page 2Linked to original sources
PubMed1998

CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity.

Recent data indicate that the cell surface glycoprotein CD5 functions as a negative regulator of T cell receptor (TCR)-mediated signaling. In this study, we examined the regulation of CD5 surface expression during normal thymocyte ontogeny and in mice with developmental and/or signal transduction defects. The results demonstrate that low level expression of CD5 on CD4(-)CD8(-) (double negative, DN) thymocytes is independent of TCR gene rearrangement; however, induction of CD5 surface expression on DN thymocytes requires engagement of the pre-TCR and is dependent upon the activity of p56(lck). At the CD4(+)CD8(+) (double positive, DP) stage, intermediate CD5 levels are maintained by low affinity TCR-major histocompatibility complex (MHC) interactions, and CD5 surface expression is proportional to both the surface level and signaling capacity of the TCR. High-level expression of CD5 on DP and CD4(+) or CD8(+) (single positive, SP) thymocytes is induced by engagement of the alpha/beta-TCR by (positively or negatively) selecting ligands. Significantly, CD5 surface expression on mature SP thymocytes and T cells was found to directly parallel the avidity or signaling intensity of the positively selecting TCR-MHC-ligand interaction. Taken together, these observations suggest that the developmental regulation of CD5 in response to TCR signaling and TCR avidity represents a mechanism for fine tuning of the TCR signaling response.

Animals↗
PubMed1998

T cell development in mice lacking all T cell receptor zeta family members (Zeta, eta, and FcepsilonRIgamma).

The zeta family includes zeta, eta, and FcepsilonRIgamma (Fcgamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4+ and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fcgamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fcgamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta-/- and zeta/eta-/--Fcgamma-/- mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fcgamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.

Animals↗
PubMed1998

Microscale titrimetric and spectrophotometric methods for determination of ionization constants and partition coefficients of new drug candidates.

This study describes the adaptation of conventional titrimetric and spectrophotometric techniques to a microscale for the determination of drug ionization constants (pKa) and partition coefficients (log P). The apparatus for determining pKa and compound purity (or equivalent weight) consists of a three-port conical glass microvial maintained at 25 degrees C, a pH microelectrode, and a microinjection pump equipped with a 10 microL gastight syringe for titrant delivery. Sample mixing and protection from atmospheric CO2, which is particularly important at the microscale, is accomplished using a fine stream of water-saturated N2 bubbles. Simple titrimetric procedures combined with ionic equilibria models which allow the accurate determination of pKa and purity (or equivalent weight) using sample sizes in the microgram range and solution volumes of 10-100 microL were developed and validated using acetic acid and tromethamine. Simultaneous determinations of pKa, purity or equivalent weight, and octanol/water partition coefficient were shown to be possible from a single sample of a test solute by adapting the pH-metric technique to a microscale. Using benzoic acid as a model compound, a pKa of 4.24 and octanol/water partition coefficient of 64 were obtained, in close agreement with the literature values. The principles employed in titrimetric analysis were also applied to demonstrate the spectrophotometric determination of benzoic acid's pKa and partition coefficient using only 6 micrograms of compound. The microscale titration method was then used to determine the two pKa values of an "unknown" diprotic acid containing a carboxyl and an aromatic SH group. The phenyl thiol pKa was confirmed using the microscale spectrophotometric procedure.

1-Octanol↗
PubMed1998

Visual-motor, visual-perceptual, and fine motor outcomes in very-low-birthweight children at 5 years.

The prevalence and severity of visual-motor deficits and the relation of visual-motor function to visual perception and fine motor skills was examined in a group of 83 neurologically and intellectually normal (IQ >84) very-low-birthweight (VLBW) children at age 5. Fifteen children (17%) had below average visual motor scores (<1SD below mean). While relatively few children (N=9) had below average scores in visual perception (11%), 58 (71%) had below average scores for fine motor skills. Nineteen (23%) were considered impaired (<1.5SD); of these, eight were severely impaired (<2SD). Fine motor scores were significantly lower in children who had been born <28 weeks' gestation, with hyaline membrane disease, or had required a longer period of ventilation. There was significant correlation between visual-motor and fine motor scores (r = 0.50, P < 0.001) and between visual-motor and visual perception scores (r = 0.42, P < 0.001). The implications of these findings and management of these 'normal' children need further research. Previous reports of visual-motor dysfunction in school-age VLBW children could be related to fine motor difficulties.

Apgar Score↗
PubMed1997

Complications of central venous access devices in children with and without cancer.

OBJECTIVE: Complications of indwelling central venous access devices (CVAD) were assessed in 63 children with cancer and 35 without cancer. METHODOLOGY: Central venous access devices placed surgically in 1991 were reviewed for complications. RESULTS: In cancer patients, the median CVAD duration was 211 days (range 9-924), compared to 37 days (range 3-339) in the non-cancer patients. Although significantly more CVAD, 41 of 72 (57%), were infected in the cancer patients compared to 14 of 40 (35%) CVAD in the non-cancer patients (OR = 2.46, 95% CI 1.03-5.93), the rate of line infection in cancer patients was lower: 2.8 per 1000 catheter days compared with 7.6 per 1000 in non-cancer patients (P = 0.0014). Infection was significantly more common in intensive chemotherapy cancer patients (P = 0.0002). CONCLUSIONS: Treating infected CVAD with antibiotics or hydrochloric acid (HCl), clearing occluded lines with streptokinase/HCl and repairing fractured lines, when successful, resulted in a considerable gain in the number of days of use for the CVAD.

Adolescent↗
PubMed1996

Modification of the extracellular matrix following myocardial infarction monitored by FTIR spectroscopy.

Comparison of mid- and near-infrared spectra of control and infarcted rat ventricular tissue reveals the presence of absorptions in infarcted tissue which are highly characteristics of collagen, indicating large scale deposition of type I collagen in the myocardium following infarction. These results demonstrate that IR spectroscopy may be used to rapidly monitor the modifications of the extracellular matrix associated with myocardial infarction.

Animals↗
PubMed1995

Neurodevelopmental outcome in very low birthweight infants with necrotizing enterocolitis requiring surgery.

OBJECTIVE: To assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome. METHODOLOGY: Neurodevelopmental outcome of 20 very low birthweight (VLBW) infants who developed NEC requiring surgery was compared with 40 matched infants controlled for gestation, birthweight, and year of admission. Twenty-nine VLBW infants who developed NEC and did not require surgery were also compared. RESULTS: Infants with NEC needing surgery were of 26 +/- 2 weeks gestation and weighted 892 +/- 192 g at birth. Infants with NEC managed medically were of higher gestation (27 +/- 2 weeks) but similar birthweights. More infants with NEC requiring surgery required inotropic support. At follow up, NEC surgery infants had a significantly higher incidence of developmental morbidity. 11 of 20 compared with 11 of 40 matched controls (Fisher's exact test P = 0.0493), and six of 29 infants with NEC managed medically (Fisher's exact test P = 0.0174). CONCLUSIONS: These findings stress the importance for close follow up for neurodevelopmental sequelae in VLBW infants who have had NEC requiring surgery.

Blindness↗
PubMed1994

Neonatal subependymal cysts detected by sonography: prevalence, sonographic findings, and clinical significance.

OBJECTIVE: Cranial sonography in neonates occasionally shows subependymal cysts. These cysts may be due to a variety of pathologic disorders, but they also occur as an "isolated" condition without an obvious cause in some patients. Assessment of the clinical significance of these lesions has been difficult because of the limited duration of follow-up, the informal nature of neurodevelopmental evaluation, and the heterogeneous cohort of patients previously reported. Accordingly, the purposes of this study were to provide more complete and longer neurodevelopmental followup and to describe the prevalence and sonographic characteristics of isolated subependymal cysts detected on cranial sonograms in neonates. MATERIALS AND METHODS: In a 4 1/2-year period, more than 4000 cranial sonograms were obtained at our institution. We retrospectively determined that 17 neonates (59 studies) had sonographic evidence of an isolated subependymal cyst. A high-resolution real-time mechanical sector transducer was used to obtain the sonograms. No subjects had clinical or sonographic evidence of intercurrent hemorrhage, infarct, infection, or congenital abnormalities. Neurodevelopmental outcome was independently determined. In particular, premature infants who weighed less than 1500 g at birth were longitudinally assessed by a multidisciplinary developmental team. A general quotient was derived in nine subjects by using the Griffith Mental Developmental Scales. RESULTS: Subependymal cysts were often tear shaped, 2-11 mm in size, and located either at the caudothalamic groove or along the anterior aspect of the caudate nucleus. Most subjects (n = 15) who had the cysts were born prematurely (mean gestational age, 31 weeks; range, 25-34 weeks). Results of follow-up were available in 14 infants 2-41 months old (mean, 22 months; median, 21 months). Development was considered to be normal in 13 of the 14 subjects; one term infant referred because of mild dysmorphic features had a mild global delay. The general quotient for corrected age, determined in nine subjects, had a mean of 111 (range, 103-120; normal, > 83). Fifteen neonates had at least two cranial sonographic examinations. In seven patients, serial examinations showed that cysts had resolved or diminished in size (on average 23 weeks after the initial sonographic study). In the other eight, no change in the size of the cyst was observed, but the mean interval between the first and last sonograms was only 14 days. CONCLUSION: Cranial sonograms of neonates occasionally show isolated subependymal cysts, usually in premature infants. In most cases, no serious neurodevelopmental complications occur. Many cysts resolve after a variable period.

Brain Diseases↗
PubMed1993

Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.

Barth syndrome is an X-linked disorder characterised by cardioskeletal myopathy of variable severity usually fatal in childhood, and neutropenia. We ascertained a large pedigree with affected males in 3 generations. All affected males had dilated cardiomyopathy, with endocardial fibroelastosis (EFE) in some. The locus for Barth syndrome in this family was found to be closely linked to DXS52 (z = 2.78, theta = 0.0). The family was nonrecombinant for DXS52 in distal Xq28, but recombinant for DXS374 which maps proximal to DXS52. This localised Barth syndrome distal to DXS374, confirming a previous localisation to distal Xq28. As yet there is no evidence for genetic heterogeneity of Barth syndrome.

Cardiomyopathies↗
PubMed1992

Necrotizing enterocolitis in a perinatal centre.

Thirty-five neonates developed radiologically proven necrotizing enterocolitis (NEC) over a 40 month period. They were 28 +/- 2 weeks gestation, and weighted 1094 +/- 411 g at birth. Eighteen infants (51%) required surgery and three (8.5%) died. The incidence was 6.7% in the very low birthweight (VLBW) infants. A large proportion of NEC (60%) presented beyond 10 days of life. An inverse relationship between gestation and age of onset was observed. The age of presentation was 22 +/- 13 days (range 10-53 days) for the 18 infants less than or equal to 28 weeks compared with 7 +/- 5 days for those over 28 weeks (P less than 0.01). Five NEC infants had bacteraemia which occurred 2-7 days prior to gastrointestinal symptoms of NEC, and four were staphylococcal. Compared with infants controlled for gestation, there was no significant differences observed in perinatal events or feeding history. We concluded that an immature gastrointestinal system is vulnerable to NEC even beyond the early neonatal period.

Enterocolitis, Pseudomembranous↗
PubMed1992

Treatment with hypertonic dextrose and insulin in severe hyperkalaemia of immature infants.

Over a three-year period, 12 infants received dextrose/insulin infusions for severe hyperkalaemia from a mean age of 24 h. The infants were born after 24 to 26 weeks of gestation and weighed 730 +/- 172 g (mean +/- SD) at birth. Serum potassium concentration ranged from 7.4 to 8.4 mmol/l (7.7 +/- 0.4 mmol/l; mean +/- SD). Four had cardiac arrhythmias. All infants showed an initial response, serum potassium concentration decreased below 6.5 mmol/l in 5 +/- 2 h. In two infants, rebound hyperkalaemia occurred and was resistant to treatment; both infants died, one during an exchange transfusion. In the other 10 infants, infusions were ceased at a mean postnatal age of 53 h. Hyperglycaemia was the major problem during infusion and was resistant to increases in insulin concentrations. Normoglycaemia was achieved in 10 infants. The hypertonic solution consisted of a dextrose/insulin ratio of 2.2 +/- 0.6 g/IU, which delivered glucose at a rate of 0.46 +/- 0.15 g/kg/h, in addition to the pre-existing stable maintenance glucose intake.

Blood Glucose↗
PubMed1991

Evaluation of bayesian forecasting for individualized gentamicin dosage in infants weighing 1000 g or less.

We evaluated the use of Bayesian forecasting for gentamicin therapy in outborn infants weighing 1000 g or less irrespective of postnatal age. Dosages were individualized using a computer program, guided by early serum gentamicin assays after a loading dose and a database of population kinetics. Steady-state gentamicin levels achieved were compared with those from a regimen based on guidelines. A total of 26 gentamicin courses were individualized in 19 infants of 22 to 33 weeks' gestation, weighing 500 to 1000 g at 1 to 41 days of age. All steady-state trough levels were between 1 and 2.4 mg/L; peak levels were between 4.4 and 9.3 mg/L. The 95% confidence intervals were in almost identical ranges. The prevalence of toxic and suboptimal trough levels was less when compared with that of 23 gentamicin courses based on guidelines in 17 control infants. We conclude that early individualized gentamicin dosage over a range of postnatal age is a practical alternative and serum level distributions appear superior.

Bayes Theorem↗
PubMed1991

Effect of short-term muscle relaxation on neonatal plasma volume.

OBJECTIVES: To study the effect of pancuronium-induced muscle relaxation on circulating plasma volume. DESIGN: A prospective, controlled study. Consecutive infants who were paralyzed with pancuronium and a comparative group who were not paralyzed during mechanical ventilation were studied. SETTING: Neonatal ICU of a regional referral university-affiliated hospital. PATIENTS: Newborn infants weighing greater than 1700 g who required respiratory assistance within 24 hrs of birth and who were free of congenital heart disease, sepsis, or blood loss were eligible for entry into the study. Infants who received colloid infusions during the study period were excluded. A total of 17 consecutive infants (nine paralyzed and eight nonparalyzed control infants) were studied. Four paralyzed infants and one nonparalyzed infant received colloid infusions before the completion of the study and were excluded from the final analysis. MEASUREMENTS: Plasma volume was measured three times in the paralyzed infants: a) immediately before the first dose of pancuronium, b) after 12 to 24 hrs, and c) greater than or equal to 12 hrs after the return of muscle activity, but before extubation. Plasma volume in the nonparalyzed, control infants was measured at the time of intubation, 12 to 24 hrs after commencing mechanical ventilation, and 12 hrs after extubation. Plasma volume was measured using the Evans blue dye dilution technique. RESULTS: There were no changes in the plasma volume or blood volume in the three measurements among both the paralyzed and nonparalyzed infants. CONCLUSION: Pancuronium-induced muscle relaxation in mechanically ventilated newborn infants weighing greater than 1700 g did not alter circulating plasma volume in 24 hrs.

Evans Blue↗
PubMed1991

A new system for location of endotracheal tube in preterm and term neonates.

A randomized, controlled trial was conducted to evaluate a new noninvasive system for placement of the endotracheal tube, based on a magnetic field interference-sensing technique. Seventy-two neonates treated by the standard technique were compared with 70 treated by the new system (TRACH MATE), with radiographic localization as the standard. As judged by the author(s) on the morning after the intubation, correct initial placement was achieved in 69 (78%) of 88 intubations using the new system, compared with 71 (66%) of 107 using the standard technique (Fisher's Test, one-tailed, P = .044). Repositioning was actually done in 23 (26%) of 88 TRACH MATE intubations, compared with 42 (39%) of 107 standard intubations (Fisher's test, one-tailed; P = .037). Intubation of the right main bronchus occurred in 7 standard intubations, but in none of the TRACH MATE intubations (Fisher's test, one-tailed; P = .014). Endotracheal tube position (high, low, or appropriate) was correctly determined by TRACH MATE in 77 (90%) of 85 intubations; the position was not recorded on three occasions. No differences in the number of complications (eg, unplanned extubations, distal displacement, subglottic stenosis) were found between the two groups. It is concluded that the TRACH MATE technique is superior to the standard clinical method in initial placement of the endotracheal tube.

Humans↗
PubMed1990

Cerebral blood-flow velocity patterns in post-hemorrhagic ventricular dilation.

To evaluate the effect of ventricular dilation (VD) on cerebral hemodynamics, serial cerebral bloodflow velocity patterns from the anterior and middle cerebral, and circle of Willis arteries were examined by range-gated, pulsed Doppler sonography in premature infants developing post-hemorrhagic VD. Nine infants (25 to 30 weeks gestation) without a patent ductus arteriosus were studied until resolution of VD. Forty-nine cranial sonograms from all nine infants were reviewed independently and grouped cross-sectionally into mild, moderate and severe VD prior to shunt. The corresponding pulsatility index (PI) showed a consistent trend of increase with VD in all three studied vessels. In six infants, absent or reversed diastolic flow was observed at the height of VD. Four of these infants required V-P shunt. Immediate fall in PI occurred in all three vessels. Serial measurement of PI during VD reflects global changes in cerebrovascular resistance. Results confirmed PI could be a useful index in monitoring cerebral hemodynamic changes.

Cerebral Hemorrhage↗
PubMed1990

Regional cerebral blood flow velocity patterns in newborn infants.

Using range-gated pulsed Doppler sonography, cerebral blood flow velocity (CBFV) waveforms from the anterior cerebral artery (ACA), middle cerebral artery (MCA) and circle of Willis artery (CW) were examined in a total of 34 newborn infants. We compared the pulsatility index (PI) from the three cerebral arteries sampled in 10 term and 10 preterm (29 +/- 2 weeks) newborn infants without a history of perinatal asphyxia or intracranial pathology. The Pl in the ACA ranged from 0.60 to 1.03. There were no significant differences in Pl between the three vessels by paired comparisons. The Pl of the MCA differed from that of the ACA by 0.00 +/- 0.05. The variation coefficient (CV) was 7%. For CW with ACA, the difference was 0.00 +/- 0.04 and CV was 6%. Both intra- and interexaminer variation in Pl measurements were studied in another 14 infants. The variation coefficients were 5-8% for all three cerebral arteries. We showed that CBFV waveform patterns were similar in regional cerebral arteries, with Pl being a consistent CBFV index. In normal cerebral circulation, the intervessel Pl differences were within observer variations. Deviation from this may suggest abnormal regional cerebral haemodynamics.

Blood Flow Velocity↗
PubMed1990

Widened subarachnoid space in pre-discharge cranial ultrasound: evidence of cerebral atrophy in immature infants?

The authors examined the incidence of widened subarachnoid spaces (SAS) among 75 infants with birthweights less than or equal to 1250g, and their significance in developmental outcome. Nine of 30 infants with gestations less than or equal to 27 weeks had widened SAS in their pre-discharge ultrasound scans. Three of the nine, including two with periventricular leukomalacia (PVL), had late-onset ventricular enlargement, unrelated to intraventricular haemorrhage (IVH): all three were developmentally impaired. The other six infants without ventricular enlargement developed normally, including one with IVH. Five of the remaining 21 infants with gestations less than or equal to 27 weeks and without widened SAS were developmentally impaired. Widened SAS was not associated with a significantly increased risk of developmental impairment; ventricular enlargement and PVL were the only significant factors. The authors conclude that an isolated finding of widened SAS is not predictive of impairment in immature infants.

Atrophy↗