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Biomedical subjects

A K Wong

Publications and source records attributed to A K Wong.

At least 19 recordsLinked to original sources
PubMed1995

Usefulness of dobutamine stress echocardiography for the prospective identification of the physiologic significance of coronary narrowings of moderate severity in patients undergoing evaluation for percutaneous transluminal coronary angioplasty.

Dobutamine stress echocardiography (DSE) was performed after coronary angiography to evaluate the need to perform percutaneous transluminal coronary angioplasty (PTCA) for 46 stenoses of moderate severity (50% to 80%) in 46 patients. Patients were divided into 2 groups according to the DSE results in the distribution of the coronary artery with the lesion of moderate severity: group I (n = 32) were those without inducible myocardial ischemia; PTCA was not performed. Group II (n = 14) were those who exhibited myocardial ischemia; PTCA was performed in 12. The 2 groups were comparable in terms of clinical characteristics. Follow-up DSE was performed < or = 48 hours after PTCA, at 3 months, and 6 to 12 months after the first DSE. In group I at 3 months, DSE results were still negative in the distribution of the vessel with the moderately severe lesion in 24 patients; only 1 patient had a positive result, and 8 patients who refused DSE remained clinically stable. At 6 to 12 months (mean 7 +/- 2), 26 patients had negative study results; 3 patients who refused follow-up DSE remained clinically stable. In group II, 12 of 14 patients with inducible ischemia on the initial DSE underwent PTCA. Early follow-up DSE (< or = 48 hours) was negative in 7, and 4 had persistent inducible wall motion abnormalities in the myocardium subtended by the coronary artery in which the PTCA had been performed; 1 study was not performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Measuring diversity: experimental design of combinatorial libraries for drug discovery.

Screening synthetic combinatorial libraries, such as mixtures of oligo(N-substituted)glycines, facilitates rapid drug lead discovery and optimization by vastly increasing the number of candidate molecules made and tested. Discovery efficiency and productivity can be further improved by using experimental design to maximize molecular diversity for a given library size or to bias the library with key features for a specific receptor. We describe new methods to quantify molecular diversity using descriptors that characterize lipophilicity, shape and branching, chemical functionality, and specific binding features. Experimental design methods select sets of side chains that are diverse in these properties, and "flower plots" allow the diversity to be graphically compared. We also quantify the overall diversity accessible to different families of combinatorial chemistry.

Drug Design↗
PubMed1995

v-Abl-mediated apoptotic suppression is associated with SHC phosphorylation without concomitant mitogen-activated protein kinase activation.

A temperature-sensitive mutant of the v-Abl protein has previously been shown to exhibit tyrosine protein kinase activity in Interleukin 3 (IL-3)-dependent IC.DP cells grown at the permissive temperature (32 degrees C) but not at the restrictive temperature (39 degrees C). These IC.DP cells are dependent on IL-3 for suppression of apoptosis at 39 degrees C, but at 32 degrees C cells will survive without added growth factor. Both IL-3 and v-Abl stimulated the tyrosine phosphorylation of SHC and GTPase-activating protein. However, while IL-3 stimulated similar levels of tyrosine phosphorylation in p46shc and p52shc, v-Abl preferentially phosphorylated p52shc, an event that occurred within 1 h of temperature switch. v-Abl also differentially associated with p46shc in a temperature-independent manner. In contrast, only IL-3 stimulated detectable increases in both myelin basic protein kinase and mitogen-activated protein (MAP) kinase kinase in in vitro assays, although in more specific MAP kinase activity assays a very slight increase in the activity of this enzyme was observed after 6 h at the permissive temperature. Time course studies suggest that phosphorylation and association of SHC with v-Abl is insufficient to lead to significant activation of MAP kinase and that activation of the MAP kinase kinase/MAP kinase pathway is not required for apoptotic suppression.

Animals↗
PubMed1995

Post-tonsillectomy infiltration with bupivacaine reduces immediate postoperative pain in children.

Pain management after tonsillectomy in children remains a dilemma for the anaesthetist. A previous study demonstrated that the administration of lidocaine 1% topical spray to the peritonsillar fossae before tracheal extubation provided considerable immediate postoperative pain relief in infants and children. However, the pain relief was of short duration. We were hopeful that the use of bupivacaine would offer more prolonged pain relief because of its pharmacological characteristics. Therefore, this study was designed to compare the effects of bupivacaine 0.5% with 1:200,000 epinephrine administered after tonsillectomy either as topical spray or submucosal infiltration on postoperative pain in children. Forty-three patients aged two to ten years were randomized into three groups after tonsillectomy was performed. Group (1) received 0.5 ml.kg-1 normal saline spray; (2) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine peritonsillar infiltration in a similar volume to Group 1 and; (3) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine spray to both tonsillar beds. The patients in each group were compared postoperatively with regard to the quality of pain control using the Objective Pain Score, and their analgesic requirements. Peritonsillar infiltration of bupivacaine provided superior immediate postoperative analgesia as reflected by lower recovery room pain scores (P < 0.05) and opioid requirements (P < 0.01). Ward pain scores and analgesic requirements were similar among groups. Peritonsillar infiltration of bupivacaine 0.5% with 1:200,000 epinephrine provides better post-tonsillectomy pain control in the immediate postoperative period than bupivacaine spray or placebo.

Anesthetics, Local↗
PubMed1995

A comparative study of postoperative complications associated with the modified Indiana pouch in elderly versus younger patients.

PURPOSE: We defined the nature and risk of complications associated with the modified Indiana pouch in patients older than 75 years. MATERIALS AND METHODS: We analyzed the clinical course of 25 elderly patients and a control group of 25 selected randomly from the cohort of those younger than 75 years. All patients underwent the modified Indiana pouch procedure. Charts were reviewed for type of operation, mean patient age, length of hospital stay, medical conditions, and early and late morbidity and mortality. Comparisons were made between the 2 groups. RESULTS: Simultaneous cystectomy or anterior exenteration was performed in 84% and 95% of patients in the elderly and younger groups, respectively. Mean age was 78.5 years in the elderly and 59.3 years in the younger group. Medical illnesses and early postoperative complication rates did not differ significantly between the 2 groups. Mean hospital stay was increased but not significantly in the elderly group (12.4 versus 11.1 days). There were 2 perioperative deaths in the elderly group (8%) and 1 in the control group (4%). Mean followup was 24.5 months (range 4 to 64) in the elderly versus 29.5 months (range 6 to 69) in the younger group. Late complications with the pouch were also similar (16% in the elderly and 12% in the control group). Of the elderly patients 9 died (intercurrent medical disease in 1 and cancer progression in 8) compared to 4 in the younger group (intercurrent medical disease in 1 and cancer progression in 3). Of the elderly patients 13 are alive (mean age 81 years) with a well functioning continent diversion. CONCLUSIONS: The modified Indiana pouch can be created with acceptable postoperative morbidity and mortality in elderly patients, and it provides an excellent functional result.

Age Distribution↗
PubMed1993

A multiple sequence comparison method.

This article presents a new method for the comparison of multiple macromolecular sequences. It is based on a hierarchical sequence synthesis procedure that does not require any a priori knowledge of the molecular structure of the sequences or the phylogenetic relations among the sequences. It differs from the existing methods as it has the capability of: (i) generating a statistical-structural model of the sequences through a synthesis process that detects homologous groups of the sequences, and (ii) aligning the sequences while the taxonomic tree of the sequences is being constructed in one single phase. It produces superior results when compared with some existing methods.

Amino Acid Sequence↗
PubMed1992

A survey of multiple sequence comparison methods.

Multiple sequence comparison refers to the search for similarity in three or more sequences. This article presents a survey of the exhaustive (optimal) and heuristic (possibly sub-optimal) methods developed for the comparison of multiple macromolecular sequences. Emphasis is given to the different approaches of the heuristic methods. Four distance measures derived from information engineering and genetic studies are introduced for the comparison between two alignments of sequences. The use of entropy, which plays a central role in information theory as measures of information, choice and uncertainty, is proposed as a simple measure for the evaluation of the optimality of an alignment in the absence of any a priori knowledge about the structures of the sequences being compared. This article also gives two examples of comparison between alternative alignments of the same set of 5SRNAs as obtained by several different heuristic methods.

Algorithms↗
PubMed1992

Structural remodeling of human myocardial tissue after infarction. Quantification with ultrasonic backscatter.

BACKGROUND: Remodeling of myocardial tissue after infarction may culminate in the development of either a well-healed scar or a thin, expanded heart wall segment that predisposes to ventricular aneurysm formation, congestive heart failure, or ventricular tachycardia. The three-dimensional architecture of mature human infarct tissue and the mechanisms that determine it have not been elucidated. We have previously shown that quantitative ultrasonic backscatter can be used to define the transmural organization of human myofibers in the normal ventricular wall by measuring the dependence of backscatter on the angle of insonification, or ultrasonic anisotropy. We propose that measurement of ultrasonic anisotropy of backscatter may permit quantitative characterization of the transmural architecture of tissue from areas of myocardial infarction and facilitate identification of fundamental mechanisms of remodeling of the ventricular wall. METHODS AND RESULTS: We measured integrated backscatter in 33 transmural sections from 12 cylindrical biopsy specimens (1.4-cm diameter) sampled from central regions of mature infarction in six explanted fixed human hearts. Tissue samples were insonified in two-degree steps around their entire circumference at successive transmural levels with a 5-MHz broad-band piezoelectric transducer. Backscatter radio frequency data were gated from the center of each specimen, and spectral analysis was performed on the gated radio frequency for the computation of integrated backscatter. Histological morphometric analysis was performed on each specimen for determination of the predominant fiber orientation and the percentage of tissue infarcted at consecutive transmural levels. The average percentage of tissue infarcted for all transmural levels was 49 +/- 3% (range, 13-80%). Histological attributes varied from patchy fibrosis to extensive confluent zones of scar tissue. The angle-averaged integrated backscatter for all transmural levels in infarct tissue was approximately 5 dB greater than that previously measured in normal tissue in our laboratory (-48.3 +/- 0.5 versus -53.4 +/- 0.4 dB, infarct versus normal). Marked anisotropy of backscatter was observed in tissue from areas of infarction and was characterized by a sinusoid-like dependence on the angle of insonification at each transmural level. Insonification perpendicular to infarct fibers yielded values for integrated backscatter 14.8 +/- 0.5 dB greater than those for insonification parallel to these fibers. Juxtaposition of the sinusoid-like anisotropy functions from all consecutive transmural levels demonstrated a progressive shift in the orientation of scar tissue elements from epicardial to endocardial levels of 14.6 +/- 1.5 degrees/mm of tissue. The transmural shift in fiber orientation per millimeter of tissue from the area of infarction exceeded that previously measured for normal tissue (9.2 +/- 0.7 degrees/mm) by 59%. This marked augmentation in angular shift per millimeter of tissue results from a generalized structural rearrangement (or reorientation) of fibers across the entire ventricular wall in the infarct zone that we hypothesize is determined in part by dynamic mechanical forces, imposed by the surrounding functional normal tissue, that tether the "infarcted" tissue. CONCLUSIONS: Myocardial tissue from areas of myocardial infarction manifests substantial anisotropy of ultrasonic scattering that may be useful for quantitative characterization of the alignment and overall three-dimensional anatomic organization of mature infarct scars.

Biopsy↗
PubMed1992

Detection of unique transmural architecture of human idiopathic cardiomyopathy by ultrasonic tissue characterization.

BACKGROUND: Noninvasive approaches to the evaluation of idiopathic cardiomyopathy are limited. Recent work from our laboratory has used quantitative ultrasound to define the three-dimensional structure of normal human myocardium and the myocardial remodeling associated with infarction. Our goal was to define the role of ultrasonic tissue characterization for detection of specific alterations in the three-dimensional transmural architecture of idiopathic dilated cardiomyopathy. METHODS AND RESULTS: We measured frequency-dependent backscatter from 22 cylindrical biopsy specimens from nine explanted fixed hearts of patients who underwent heart transplantation for idiopathic cardiomyopathy, seven specimens from normal portions, and 12 specimens of infarcted tissue from six explanted fixed human hearts. Consecutive transmural levels from each specimen were insonified with a 5-MHz broadband transducer. The dependence of apparent (uncompensated for attenuation) backscatter, B(f), on frequency (f) was computed from radiofrequency (rf) data as: magnitude of B(f)2 = afn, where n is an index that reflects in part the size of the dominant scatterers in myocardial tissue. Myofiber diameter and percentage fibrosis were determined at each transmural level for each specimen. For cardiomyopathic tissue, the frequency dependence of backscatter (n) increased progressively from epicardial to endocardial (0.02 +/- 0.37 to 1.01 +/- 0.12, p less than 0.05) levels in conjunction with a progressive decrease in myofiber diameter (29.5 +/- 0.9 to 21.4 +/- 0.6 microns, p less than 0.0001). In contrast, in tissue from areas of infarction, the frequency dependence decreased progressively from epicardium to endocardium (0.91 +/- 0.20 to 0.23 +/- 0.21, p less than 0.05) in conjunction with a progressive increase in the percentage of fibrosis (23.5 +/- 9.4% to 54.5 +/- 4.9%, p less than 0.005). Normal tissue exhibited no significant transmural trend for frequency dependence, myofiber diameter, or percentage fibrosis. CONCLUSIONS: These data indicate the presence of a heterogenous transmural distribution of scattering structures associated with human idiopathic cardiomyopathy and myocardial infarction that may be detected by ultrasonic tissue characterization. The divergence of these transmural trends for frequency dependence of backscatter reflects distinct mechanisms of structural heterogeneity for different pathological processes that comprise a transmural gradation of cell size and fibrosis for idiopathic cardiomyopathy and infarction, respectively.

Cardiomyopathies↗
PubMed1991

Identification of novel single-stranded d(TC)n binding proteins in several mammalian species.

A group of single-stranded d(TC)n specific binding proteins has been detected in the nuclear extracts of several mammalian species that included mouse, human, African green monkey, chimpanzee, and Chinese muntjac. Southwestern analysis of 500 mM KCI nuclear extracts has shown that these proteins cluster in a similar size range, 55.5 to 57 kD. An additional 54 kD band was present for the three primate species examined. The single-stranded d(TC)n binding activity was confirmed with bandshift assay. Specific double-stranded binding activity for duplex d(TC)n.d(GA)n or single-stranded d(GA)n was not detected. The conservation of size distribution and d(TC)n-binding activity across the species examined indicates that this class of single-stranded binding proteins may have an important biological function in vivo.

Animals↗
PubMed1991

Isolated atrial infarction in a patients with single vessel disease of the sinus node artery.

Atrial infarction is found in approximately 17 percent of autopsy-proven cases of myocardial infarction, but is a frequently missed clinical diagnosis. The antemortem diagnosis of atrial infarction occurring in the absence of ventricular infarction has not been previously reported. We present a patient with ischemic chest discomfort associated with paroxysmal atrial fibrillation. Electrocardiographic and enzymatic changes were consistent with atrial infarction. Cardiac catheterization demonstrated single vessel critical stenosis at the origin of the sinus node artery. Combined atrial and ventricular infarction occurs frequently and should be considered in the setting of paroxysmal supraventricular arrhythmias occurring early in the course of ventricular myocardial infarction. Lone atrial infarction is a rare but distinct clinical entity. The tetrad of typical ischemic chest discomfort, paroxysmal supraventricular arrhythmia, P-Ta segment shifts, and elevated cardiac enzyme levels without evidence for ventricular infarction strongly suggests isolated atrial infarction.

Aged↗
PubMed1991

Longer, healthier and happier lives.

In Singapore an effort is being made to keep elderly people physically and mentally fit for as long as possible so that they can maintain their normal daily activities and living arrangements. In order to care for the growing proportion of older people both humanely and in a manner that society can afford, measures are being taken to encourage the revival of the extended family system whereby the elderly reside with their younger relatives. The placing of older people in institutions is being kept to a minimum, partly because they prefer to live with their children and partly because special homes are very expensive.

Aged↗
PubMed1990

The chromosomal distribution of the major and minor satellite is not conserved in the genus Mus.

The cytological distribution of the major and minor satellite first identified in Mus musculus was studied in the karyotypes of three related subspecies and two other species of the genus Mus. Both the major and minor satellite showed species dependent hybridization patterns. The major satellite is confined to the centromere region in M. musculus and related subspecies. However, in M spretus and M. caroli, the chromosomal arm regions contain this sequence class. In contrast the minor satellite is found at the kinetochore region in M. musculus and related subspecies but is distributed throughout the entire centromeric domain in M. spretus and appears to be excluded from the chromosomes of M. caroli. There is an apparent correlation between the chromosomal location of these satellites and their phylogenetic relationship. Determination of the biological roles of the major and minor satellites from M. musculus must take into account their differential chromosomal distribution in other Mus species.

Animals↗
PubMed1990

Distribution of CT-rich tracts is conserved in vertebrate chromosomes.

The distribution of d(CT)-rich pyrimidine tracts in the karyotypes of a variety of vertebrates was studied by in situ hybridization. The probe for these studies was a 56bp homopyrimidine/homopurine sequence obtained from a mouse genomic library constructed with DNA prepared from a restriction enzyme digestion of metaphase chromosomes. Single-stranded DNA nuclease digestions and two-dimensional gel analysis of topoisomers of this sequence indicated that it is capable of adopting a triplex conformation in vitro. In situ hybridization with this probe to the karyotypes of ten different vertebrate species revealed a highly conserved chromosomal distribution of d(CT)-rich tracts. These tracts are found throughout the chromosomal arms and in some karyotypes they are clustered, producing a banding pattern. However, at the resolution of the light microscope these tracts appeared to be absent from the centromeric regions of all chromosomes examined except those of chicken. The non-random distribution of these tracts to the chromosomal arm regions implies an organizational or functional role for this repeat class. It is unlikely that the 56 bp sequence type contributed to the formation of the triplex DNA structure previously detected in centromeric domains of mouse.

Animals↗
PubMed1990

Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), Pi, and [H+] were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/Pi (r = 0.94). Pi and [H+] were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%. Thus, these data demonstrate that PCr/Pi is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H+ as inhibitors of myocardial contractility during ischemia.

Adenosine Triphosphate↗
PubMed1989

Age related flow rate nomograms in a normal pediatric population.

Uroflow studies in a normal pediatric population were analysed statistically. Single studies for 511 subjects (272 boys and 239 girls) were reviewed. Nomograms relating peak flow to volume voided and age were established. An acceptable lower limit for peak flow was obtained from the data and a volume voided range was calculated so that both criteria could be used with 90% probability to define the normal voiding situation. The mean values of peak flow rate increased with volume voided in both sexes and also with age in the male population. Different sets of nomograms, which are necessary for daily clinical evaluation, are given. They define the normal values in the normal population.

Adolescent↗
PubMed1989

Body surface related flow rate nomograms in a normal pediatric population.

Uroflow studies for 511 normal pediatric subjects (272 boys, 239 girls) were analyzed statistically. Nomograms relating peak flow to volume voided and body surface were established. An acceptable lower limit for peak flow was obtained from the data and a volume voided range was calculated so that both criteria could be used with 90% probability to define the normal voiding situation. Body surface area was found to be a more reliable index than age in the establishment of nomograms. In the male population the 90% probability applied to a significantly greater volume voided reliability. In the female population mean peak flow rate rose with increased body surface. Finally, in both sexes the 10% lower limit was closer to the regression mean, allowing a tighter distribution around this value.

Adolescent↗