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Biomedical subjects

N Chan

Publications and source records attributed to N Chan.

At least 19 recordsLinked to original sources
PubMed2006

Economic burden of revision hip and knee arthroplasty in Medicare enrollees.

UNLABELLED: The economic burden to Medicare due to revision arthroplasty procedures has not yet been studied systematically. The economic burden of revisions was calculated as annual reimbursements for revision arthroplasties relative to the sum total reimbursements of primary and revision arthroplasties. We evaluated this revision burden for total hip and knee arthroplasties through investigation of trends in charges and reimbursements in the Medicare population (Parts A and B claims from 1997-2003), while taking into account age and gender effects. Mean annual economic revision burdens were 18.8% (range, 17.4-20.2%) and 8.2% (range, 7.5-9.2%) for total hip arthroplasties and total knee arthroplasties, respectively. Procedural charges increased while reimbursements decreased over the study period, with higher charges observed for revisions than primary arthroplasties. Reimbursements per procedure were 62% to 68% less than associated charges for primary and revision total hip and knee arthroplasties. The effect of age and gender on reimbursements varied by procedure type. Unless some limiting mechanism is implemented to reduce the incidence of revision surgeries, the diverging trends in reimbursements and charges for total hip and knee arthroplasties indicate that the economic impact to the Medicare population and healthcare system will continue to increase. LEVEL OF EVIDENCE: Prognostic study, level II-1 (retrospective study). See Guidelines for Authors for a complete description of levels of evidence.

Aged↗
PubMed2005

Chromosomal translocation engineering to recapitulate primary events of human cancer.

Mouse models of human cancers are important for understanding determinants of overt disease and for "preclinical" development of rational therapeutic strategies; for instance, based on macrodrugs. Chromosomal translocations underlie many human leukemias, sarcomas, and epithelial tumors. We have developed three technologies based on homologous recombination in mouse ES cells to mimic human chromosome translocations. The first, called the knockin method, allows creation of fusion genes like those typical of translocations of human leukemias and sarcomas. Two new conditional chromosomal translocation mimics have been developed. The first is a method for generating reciprocal chromosomal translocations de novo using Cre-loxP recombination (translocator mice). In some cases, there is incompatible gene orientation and the translocator model cannot be applied. We have developed a different model (invertor mice) for these situations. This method consists of introducing an inverted cDNA cassette into the intron of a target gene and bringing the cassette into the correct transcriptional orientation by Cre-loxP recombination. We describe experiments using the translocator model to generate MLL-mediated neoplasias and the invertor method to generate EWS-ERG-mediated cancer. These methods mimic the situation found in human chromosome translocations and provide the framework for design and study of human chromosomal translocations in mice.

Animals↗
PubMed2003

Acute interstitial nephritis in Singapore: a report of five cases.

Interstitial nephritis is an uncommon cause of acute renal failure. Reported incidence varies widely in the literature and may depend on several factors i.e. geographical location, diagnostic criteria, dietary, environmental factors and therapeutic practices. This is a retrospective study of biopsy proven interstitial nephritis in National University Hospital Singapore. We report five cases out of a total of 349 biopsies carried out during a five-year period between September 1997 and August 2002. Four patients presented acutely with fever and or cough. In four patients, there was exposure to traditional Chinese medications and/or drugs. Renal failure in four out of the five patients progressed rapidly, three of whom required dialysis. One patient was treated with steroids. Renal function recovered in all patients with one patient who had significant residual renal impairment after one month.

Acute Disease↗
PubMed2000

Molecular and functional characterization of protein 4.1B, a novel member of the protein 4.1 family with high level, focal expression in brain.

Brain-enriched isoforms of skeletal proteins in the spectrin and ankyrin gene families have been described. Here we characterize protein 4.1B, a novel homolog of erythrocyte protein 4.1R that is encoded by a distinct gene. In situ hybridization revealed high level, focal expression of 4.1B mRNA in select neuronal populations within the mouse brain, including Purkinje cells of the cerebellum, pyramidal cells in hippocampal regions CA1-3, thalamic nuclei, and olfactory bulb. Expression was also detected in adrenal gland, kidney, testis, and heart. 4.1B protein exhibits high homology to the membrane binding, spectrin-actin binding, and C-terminal domains of 4.1R, including motifs for interaction with NuMA and FKBP13. cDNA characterization and Western blot analysis revealed multiple spliceoforms of protein 4.1B, with functionally relevant heterogeneity in the spectrin-actin and NuMA binding domains. Regulated alternative splicing events led to expression of unique 4. 1B isoforms in brain and muscle; only the latter possessed a functional spectrin-actin binding domain. By immunofluorescence, 4. 1B was localized specifically at the plasma membrane in regions of cell-cell contact. Together these results indicate that 4.1B transcription is selectively regulated among neuronal populations and that alternative splicing regulates expression of 4.1B isoforms possessing critical functional domains typical of other protein 4.1 family members.

Amino Acid Sequence↗
PubMed1997

Pheochromocytoma manifesting with shock presents a clinical paradox: a case report.

A 46-year-old man presented with shock and adult respiratory distress syndrome. Investigations revealed an adrenal mass that was diagnosed, by fine-needle aspiration biopsy, as pheochromocytoma. Because biopsy is contraindicated in patients with pheochromocytoma, this confusing presentation underscores the value of excluding this diagnosis by biochemical means before performing fine-needle aspiration of adrenal tumours.

Adrenal Gland Neoplasms↗
PubMed1997

Chemical synthesis of Haemophilus influenzae glycopeptide conjugates.

A simple procedure for conjugating synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b, poly-3-beta-D-ribose-(1,1)-D-ribitol-5-phosphate (sPRP) to linear peptides is described. The procedure consists of (i) reacting the amino group of amino-heptyl sPRP with m-maleimidobenzoyl-N-hydroxysuccinimide (MBS) in phosphate buffer, pH 7.5; (ii) selectively coupling the MBS-modified sPRP to the sulfhydryl group of the cysteine residue of peptides containing functional T-helper cell epitope(s). The glycopeptide conjugates were purified by gel filtration chromatography, biochemically characterized, and elicited protective level of anti-PRP antibody responses in rabbits.

Amino Acid Sequence↗
PubMed1997

A strategy for rational design of fully synthetic glycopeptide conjugate vaccines.

The present study describes a strategy to rationally design fully synthetic glycopeptide conjugate vaccines. Glycopeptide immunogens were constructed by coupling synthetic oligosaccharides comprising repeating units of synthetic 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate (sPRP) to synthetic peptides containing potent T-helper cell determinants and B-cell epitopes of the Haemophilus influenzae type b (Hib) outer membrane proteins (OMPs) P1, P2, and P6. Rabbit immunogenicity studies revealed that some of these fully synthetic glycoconjugates were capable of eliciting high titers of both anti-PRP and anti-OMP immunoglobulin G antibodies. In addition, we systematically investigated the factors which could influence their immunogenicity. We observed that the magnitude of the anti-PRP antibody response markedly depended on the relative spatial orientation of sPRP and T-cell epitopes, the anti-PRP antibody response was enhanced when a multiple antigenic peptide was used as a carrier, the anti-PRP antibody response was optimal for three PRP repeating units, and lipidation of peptide-PRP conjugates had a minimal effect on the magnitude of the anti-PRP antibody response. The results of this study clearly demonstrate that coupling a carbohydrate hapten to a peptide can provide T-cell help and convert it into a T-cell-dependent antigen. The antisera raised against these conjugates were also found to be protective against Hib infection in the infant rat model of bacteremia.

Amino Acid Sequence↗
PubMed1995

Location of nitric oxide synthase in the developing avian ciliary ganglion.

A study has been made of the distribution of nitric oxide synthase (NOS) in the developing avian ciliary ganglion. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity first appeared in ciliary neurones at embryonic day 10 (E10). The number of NADPH-d positive neurones appeared maximal at this age and thereafter declined; at post hatched day 4 (P4) these neurones were found predominately in the periphery of the ganglion. At the light microscope level the NADPH-d stain appeared throughout the cell soma of the ciliary neurones. This was confirmed using tissue culture techniques. Ultrastructural delineation of horseradish peroxidase-labelled NOS antibodies was also found in the calyx where it was bound to the membranes of the endoplasmic reticulum as well as to the outer membranes of mitochondria. This distribution of NOS in the soma and calyx is consistent with the physiological role of NO as a co-transmitter and retrograde messenger that regulates the quantal secretion of the principal transmitter, acetylcholine, from the calyx.

Aging↗
PubMed1993

An unusual form of pulmonary aspergillosis in two patients with the acquired immunodeficiency syndrome.

Two cases of an unusual pathologic form of pulmonary aspergillosis in patients with the acquired immunodeficiency virus are reported. Each was characterized by chronic cavitary disease with involvement of small bronchioles and extension into subtending alveoli. It is suggested that this variant would best be described as chronic cavitary and invasive bronchopulmonary aspergillosis. A prominent feature in each case was the presence of numerous cytomegalovirus inclusions adjacent to the cavities and affected airways. The significance of this association is not known.

AIDS-Related Opportunistic Infections↗
PubMed1992

Renal hypoplasia and postnatally acquired cortical loss in children with vesicoureteral reflux.

We reviewed histologically 86 nephrectomy specimens from patients with vesicoureteral reflux (with or without ureterovesical obstruction) to investigate the relationship between coexisting hypoplasia and postnatally acquired cortical damage. Hypoplasia was assessed independently of the acquired cortical loss using medullary ray glomerular counting. Severe hypoplasia (glomerular number < 25% of normal) was detected in 47 of 86 patients. These patients underwent nephrectomy at a significantly younger age than those with minimal or no hypoplasia (P < 0.01). There was no significant relationship between the severity of hypoplasia and the presence or absence of obstruction. Severe acquired cortical loss was found in 68 of 86 patients. There was no significant association between the severity of cortical loss and the presence or absence of obstruction, age at nephrectomy or degree of coexisting hypoplasia. The findings suggest a strong association of hypoplasia and vesicoureteral reflux. Therefore, early postnatal presentation with minimal renal function need not necessarily reflect a failure of management but rather a pre-existing limitation of renal capacity. Furthermore, in a significant proportion of fetuses with ultrasonographic evidence of urinary tract abnormality, renal pathology may be present prior to the time at which in utero surgical intervention may be considered.

Adolescent↗
PubMed1988

Inflation of lung biopsies for frozen section.

It is widely accepted that fixation inflation of lung surgical specimens, including open lung biopsies, greatly aids histologic examination and diagnosis. This method is not, however, appropriate for frozen section material. To obviate this problem, we have inflated the specimen with the embedding medium used for frozen section. This procedure provides inflation of the lung sample, increases the ease with which the biopsy is sectioned in the cryostat, and also reduces the shattering commonly seen in standard frozen sections of lung.

Biopsy↗