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Biomedical subjects

J A Wong

Publications and source records attributed to J A Wong.

16 recordsLinked to original sources

Decreased bone mineral density in the pediatric renal transplant population.

All renal transplant recipients at our centre have had bone mineral density assessment (BMD) by DEXA scans of their lumbar spine while on the transplant waitlist and at 6-month intervals post-transplant over the past 7 yr. Risk factors for osteopenia and osteoporosis including donor source, dialysis status prior to transplantation, prior renal disease, and biopsy confirmed rejection events and their relationship to BMD of the lumbar spine were assessed. Thirty-nine children transplanted over the past 7 yr were included in this study. In total, 127 BMD longitudinal assessments were performed. From 1990 to 1997, ATG/ALG was used as antibody induction therapy. From 1997 to 2002, Basiliximab was utilized. Cyclosporin A (CyA) was the primary immunosuppressant for most children with tacrolimus as primary (n = 2) and switch for CyA failure or toxicity (n = 16). Prednisone was administered at a dose of 1 mg/kg/day for the first week and tapered to 10 mg/m2/alternate day by 1 month post-transplant. Azathioprine 1.5 mg/kg/day was continued for 1 yr and discontinued in children who were rejection free. All rejections were biopsy confirmed and treated with a prednisone pulse. Using a repeated measures regression analysis, we have found that L1-L4 BMD z score is affected by height and transplant number. It is also related to time relative to transplant in a quadratic fashion. There was an inverse relationship between advancing patient age and L1-L4 BMD z score. L1-L4 BMD z score was not related to weight, pre-existing renal disease, gender, donor source, type of renal replacement therapy prior to transplantation, or rejection events.

Adolescent↗

Insulin-independent, MAPK-dependent stimulation of NKCC activity in skeletal muscle.

Na(+)-K(+)-Cl(-) cotransporter (NKCC) activity in quiescent skeletal muscle is modest. However, ex vivo stimulation of muscle for as little as 18 contractions (1 min, 0.3 Hz) dramatically increased the activity of the cotransporter, measured as the bumetanide-sensitive (86)Rb influx, in both soleus and plantaris muscles. This activation of cotransporter activity remained relatively constant for up to 10-Hz stimulation for 1 min, falling off at higher frequencies (30-Hz stimulation for 1 min). Similarly, stimulation of skeletal muscle with adrenergic receptor agonists phenylephrine, isoproterenol, or epinephrine produced a dramatic stimulation of NKCC activity. It did not appear that stimulation of NKCC activity was a reflection of increased Na(+)-K(+)-ATPase activity because insulin treatment did not stimulate NKCC activity, despite insulin's well-known stimulation of Na(+)-K(+)-ATPase activity. Stimulation of NKCC activity could be blocked by pretreatment with inhibitors of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2) activity, indicating that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) MAPKs may be required. These data indicate a regulated NKCC activity in skeletal muscle that may provide a significant pathway for potassium transport into skeletal muscle fibers.

Adrenergic Agonists↗

Molecular and functional evidence for Na(+)-K(+)-2Cl(-) cotransporter expression in rat skeletal muscle.

Doubt has been raised about the expression of a functional Na(+)-K(+)-2Cl(-) cotransporter in rat skeletal muscle. In this study we present molecular and functional evidence for expression of a protein having the characteristics of a cotransporter. RT-PCR of RNA isolated from rat soleus muscle with primers to a conserved putative membrane-spanning domain resulted in a single product of predicted size. Sequencing of the product showed that it bears >90% homology with known rodent NKCC1 (BSC2) cotransporters. RNase protection assay of RNA isolated from the rat soleus muscle also identified this sequence. Immunologic detection of the cotransporter with two different antibodies indicated the presence of cotransporter protein, perhaps more than one, in blots of total muscle protein. Immunohistochemical detection by confocal microscopy localized the majority of expression of the protein to the muscle fibers. Functional studies of cotransport activity also indicate the appropriate sensitivity to inhibitors and ion dependence. Taken together, these data support the presence and function of Na(+)-K(+)-2Cl(-) cotransporter activity in the soleus muscle of the rat.

Animals↗

Unique 5'-end of a Na(+)-K(+)-2Cl- cotransporter-like mRNA expressed in rat skeletal muscle.

Functional evidence presented by others indicates that rat slow-twitch skeletal muscle lacks typical Na(+)-K(+)-2Cl- cotransporter activity, as determined by loop diuretic-sensitive potassium transport. This report presents a unique 5' mRNA sequence of a Na(+)-K(+)-2Cl- cotransporter-like molecule expressed in the rat soleus muscle and the deduced N-terminus of the protein. In addition to its unique 5' mRNA sequence, the coding region of the N-terminus is quite short compared with other known Na(+)-K(+)-2Cl- cotransporters. Nonetheless, the mRNA possesses conserved cotransporter-like membrane spanning domains, though one domains corresponding to a reported exon is divergent. Therefore, it appears that skeletal muscle does express a Na(+)-K(+)-2Cl- cotransporter-like mRNA that may code for a protein with atypical Na(+)-K(+)-2Cl- cotransporter properties.

Amino Acid Sequence↗

Validation of color Doppler measurements of minimum patent ductus arteriosus diameters: significance for coil embolization.

BACKGROUND: Echocardiography is sometimes performed to identify candidates for coil embolization of patent ductus arteriosus (PDA). Therefore we attempted to determine the validity of color Doppler echocardiography to accurately determine the minimum PDA diameter. METHODS AND RESULTS: We reviewed data from 27 children (median 3.8 years, range 1 to 15 years) with PDAs and measured their minimum ductal diameters by color flow Doppler echocardiography and by angiography. We found that there were significant mean differences between the color Doppler and angiographic measurements (2.7+/-0.8 vs 1.6+/-0.7 mm, P< .001) with color Doppler exceeding angiographic measurements by > or = 1.0 mm in 15 (56%) of 27 patients. More importantly, color Doppler measured a PDA > or = 4.0 mm (usually greater than that recommended for coiling) in 3 (11%) patients in whom the angiographic measurement was <4.0 mm. Correlation analysis demonstrated no correlation between the color Doppler and angiographic measurements (r2 = 0.17, P= .04, SEE = 0.2 mm). CONCLUSIONS: These data suggest that color Doppler echocardiography often overestimates the true minimum PDA diameter, therefore we recommend that a color Doppler-based recommendation that a PDA is too large for transcatheter coil occlusion not be used exclusively to exclude a patient from this treatment modality.

Adolescent↗

Division of the main pulmonary artery: suboptimal palliation for the patient with a univentricular heart.

We describe a patient in whom a thrombus formed in the distal main pulmonary artery stump after a bidirectional Glenn procedure with division of the main pulmonary artery and in whom a restrictive inlet ventricular septal defect also developed. These findings emphasize the importance of maintaining antegrade flow through the pulmonary trunk and providing dual sources of ventricular outflow with a Damus-Kaye-Stansel anastomosis in patients with a univentricular heart without pulmonary stenosis.

Anastomosis, Surgical↗

Noncompaction of the ventricular myocardium in Melnick-Needles syndrome.

A 4-year-old asymptomatic boy was referred for evaluation after being diagnosed with Melnick-Needles syndrome. Echocardiography demonstrated noncompaction of the left ventricular myocardium as an isolated cardiac finding. Though other structural cardiac defects were reported previously in this syndrome, this is the first report of this rare cardiac anomaly in this likewise rare syndrome. We postulate that this occurrence represents a primary disorder of early fetal development. Patients with Melnick-Needles syndrome should be evaluated for noncompaction of the ventricular myocardium and its potential cardiovascular dysfunction.

Child, Preschool↗

Dose-volume considerations with linear programming optimization.

A method of incorporating dose-volume considerations within the framework of conventional linear programming is presented. This method is suitable for the optimization of beam weights and angles using a conformal treatment philosophy (i.e., tailoring the high-dose region to the target volume only). Dose-volume constraints are introduced using the concept that volumes of normal tissue nearer the target volume will be allowed higher dose constraints than volumes of normal tissue distal to the target volume. Each involved normal structure is divided into high-dose and low-dose volumes. These two volume partitions are represented by constraint points with either high-dose or low-dose constraints, respectively. Optimized treatment plans for three clinical sites demonstrate that this technique meets or surpasses the original dose-volume constraints for a conformal-type treatment plan using straightforward linear programming in a time frame that is comparable to other linear programming problems.

Humans↗