Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 19 recordsLinked to original sources

PubMed2007

A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity.

BACKGROUND: Chinese herbal medicine (CHM) is a common complementary therapy used by patients with cancer for reduction of chemotherapy-induced toxic effects. This study applied the highest standard of clinical trial methodology to examine the role of CHM in reducing chemotherapy-induced toxicity, while maintaining a tailored approach to therapy. PATIENTS AND METHODS: Patients with early-stage breast or colon cancer who required postoperative adjuvant chemotherapy were eligible for the study. Enrolled patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed a combination of single-item packaged herbal extract granules. Patients received either CHM or placebo packages with a corresponding serial number. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to a typical herbal tea. The primary end points were hematologic and non-hematologic toxicity according to the National Cancer Institute Common Toxicity Criteria Version 2. RESULTS: One hundred and twenty patients were accrued at the time of premature study termination. Patient characteristics of the two groups were similar. The incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%, 44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively). Incidence of grade 2 nausea was the only non-hematologic toxicity that was significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04). CONCLUSIONS: Traditional CHM does not reduce the hematologic toxicity associated with chemotherapy. CHM, however, does have a significant impact on control of nausea.

Adult↗

PubMed2007

Anti-P. gingivalis response correlates with atherosclerosis.

Significant associations between atherosclerosis and both Porphyromonas gingivalis, a major periodontopathogen, and the respiratory pathogen, Chlamydia pneumoniae, have been shown. Many individuals with evidence of atherosclerosis demonstrate seropositivity to these pathogens. The aim of the present study was to examine the atherogenic effect of repeated immunizations with either or both of these agents, and to determine if molecular mimicry of bacterial heat-shock protein (HSP), termed GroEL, and host (h) HSP60 was involved. Atherogenesis was examined in apolipoprotein-E-deficient (-/-) mice following intraperitoneal immunizations with P. gingivalis, C. pneumoniae, P. gingivalis, and C. pneumoniae or vehicle. Lesion area in the proximal aorta and levels of serum antibodies to P. gingivalis, C. pneumoniae, and GroEL were measured. The increased pathogen burden of P. gingivalis, but not of C. pneumoniae, enhanced atherosclerosis. hHSP60 was detected in lesions, and in P. gingivalis-immunized mice, lesion development was correlated with anti-GroEL antibody levels, supporting the involvement of molecular mimicry between GroEL and hHSP60.

Animals↗

PubMed2006

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial.

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m-2 week-1 and trastuzumab: 4 mg kg-1 on day 1 as a loading dose followed by 2 mg kg-1 week-1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6-12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4-32.6). This regimen was safe: grade 3-4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005.

Adult↗

PubMed2006

[Plasma exchange therapy for steroid-unresponsive multiple sclerosis relapses: clinical experience with 16 patients].

Patients with severe multiple sclerosis (MS) relapses which do not respond sufficiently to corticosteroids can undergo escalating immunotherapy with plasma exchange. We review the course of 14 apheresis cycles in 13 adult patients and three pediatric cases from our center between 2004 and 2005. Nine cases were due to optic neuritis, five had experienced clinically isolated syndromes, and two suffered from Devic's disease. Of the adult patients, 71% had good or very good outcome. The mean time point of improvement was after the third plasmapheresis session, and early initiation of plasma exchange therapy (within 1 month after begin of relapse) was associated with better outcome. In pediatric MS, two of three patients showed clear improvement. These data argue for a very good therapeutic effect of plasma exchange if performed early and with adequate indication.

Activities of Daily Living↗

PubMed2006

Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy.

A genome-wide screen for asthma and atopy susceptibility alleles conducted in the Hutterites, a founder population of European descent, reported evidence of linkage with a short tandem repeat polymorphism (STRP) within the type I interferon (IFN) gene cluster on chromosome 9p21. The goal of this study was to identify variation within the IFN gene cluster that influences susceptibility to asthma and atopic phenotypes. We screened approximately 25 kb of sequence, including the flanking sequence of all 15 functional genes and the single coding exon in 12, in Hutterites representing different IFNA-STRP genotypes. We identified 78 polymorphisms, and genotyped 40 of these (in 14 genes) in a large Hutterite pedigree. Modest associations (0.003<P<0.05) with asthma, bronchial hyper-responsiveness (BHR), and atopy were observed with individual variants or genes, spanning the entire 400 kb region. However, pairwise combinations of haplotypes between genes showed highly significant associations with different phenotypes (P<10(-5)) that were localized to specific pairs of genes or regions of this cluster. These results suggest that variation in multiple genes in the type I IFN cluster on 9p22 contribute to asthma and atopy susceptibility, and that not all genes contribute equally to all phenotypes.

Adolescent↗

PubMed2006

Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study.

BACKGROUND: Inflammation is a significant component of atherosclerosis lesions. Bacteria, including periodontopathogens, have been demonstrated in atherosclerotic plaques and cross-reactivity of the immune response to bacterial GroEL with human heat shock protein 60 has been suggested as a link between infections and atherosclerosis. METHODS: In this study, the nature of the inflammatory infiltrate and the presence of human heat shock protein 60 and GroEL were examined in 31 carotid endarterectomy specimens. Additionally, monoclonal antibodies were used to detect the presence of six bacteria, including those implicated in periodontal disease. RESULTS: The inflammatory cell infiltrate of the lesions was dominated by CD14(+) macrophages and CD4(+) T cells. Most cells of the infiltrate as well as the endothelium were HLA-DR(+), indicating activation; however, there was an absence of CD25 expression, demonstrating that the activated T cells were not proliferating. Few CD1a(+) and CD83(+) cells were noted. Human heat shock protein 60 expression was evident on endothelial cells and cells with the appearance of smooth muscle cells and lymphocytes. GroEL and bacteria were detected within intimal cells. Chlamydia pneumoniae, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, and Actinobacillus actinomycetemcomitans were found in 21%, 52%, 34%, 34%, 41%, and 17% of arteries, respectively. CONCLUSION: These results give evidence for a specific immune response associated with atherosclerosis. Whether bacteria initiate the observed inflammation in atherosclerotic lesions is not clear; however, the present study shows that maintenance of inflammation may be enhanced by the presence of periodontopathic bacteria.

Aggregatibacter actinomycetemcomitans↗

PubMed2006

Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration.

AIM: To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT). METHODS: A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of approximately 3 mum axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed. RESULTS: 52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT. CONCLUSION: With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.

Aged↗

PubMed2005

Differences in risk factors between early and late diagnosed developmental dysplasia of the hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is common, affecting 7.3 per 1000 births in South Australia. Clinical screening programmes exist to identify the condition early to gain the maximum benefit from early treatment. Although these screening programmes are effective, there are still cases that are missed. Previous research has highlighted key risk factors in the development of DDH. OBJECTIVE: To compare the risk factors of cases of DDH identified late with those that were diagnosed early. METHODS: A total of 1281 children with DDH born in 1988-1996 were identified from the South Australian Birth Defects Register. Hospital records of those who had surgery for DDH within 5 years of life were examined for diagnosis details. Twenty seven (2.1%) had been diagnosed at or after 3 months of age and were considered the late DDH cases (a prevalence of 0.15 per 1000 live births). Various factors were compared with early diagnosed DDH cases. RESULTS: Female sex, vertex presentation, normal delivery, rural birth, and discharge from hospital less than 4 days after birth all significantly increased the risk of late diagnosis of DDH. CONCLUSIONS: The results show differences in the risk factors for early and late diagnosed DDH. Some known risk factors for DDH are in fact protective for late diagnosis. These results highlight the need for broad newborn population screening and continued vigilance and training in screening programmes.

Age Distribution↗

PubMed2005

Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.

BACKGROUND: A novel autosomal recessive condition, dilated cardiomyopathy with ataxia (DCMA) syndrome, has been identified in the Canadian Dariusleut Hutterite population, characterised by early onset dilated cardiomyopathy with conduction defects, non-progressive cerebellar ataxia, testicular dysgenesis, growth failure, and 3-methylglutaconic aciduria. OBJECTIVE: To map DCMA syndrome and identify the mutation underlying this condition. METHODS: A genome wide scan was undertaken on consanguineous Hutterite families using a homozygosity mapping approach in order to identify the DCMA associated chromosomal region. Mutation analysis was carried out on positional candidate genes in this region by sequencing. Reverse transcriptase polymerase chain reaction and bioinformatics analyses were then used to characterise the mutation and determine its effect on the protein product. RESULTS: The association of DCMA syndrome with a 2.2 Mb region of chromosome 3q26.33 was found. A disease associated mutation was identified: IVS3-1 G-->C in the DNAJC19 gene, encoding a DNAJ domain containing protein of previously unknown function (Entrez Gene ID 131118). CONCLUSIONS: The DNAJC19 protein was previously localised to the mitochondria in cardiac myocytes, and shares sequence and organisational similarity with proteins from several species including two yeast mitochondrial inner membrane proteins, Mdj2p and Tim14. Tim14 is a component of the yeast inner mitochondrial membrane presequence translocase, suggesting that the unique phenotype of DCMA may be the result of defective mitochondrial protein import. It is only the second human disorder caused by defects in this pathway that has been identified.

Abnormalities, Multiple↗

PubMed2005

Search for the lepton-number-violating decay Xi(-)-->pmu(-)mu(-).

A sensitive search for the lepton-number-violating decay Xi(-)-->pmu(-)mu(-) has been performed using a sample of approximately 10(9) Xi(-) hyperons produced in 800 GeV/c p-Cu collisions. We obtain B(Xi(-)-->pmu(-)mu(-))<4.0x10(-8) at 90% confidence, improving on the best previous limit by 4 orders of magnitude.

Journal Article↗

PubMed2005

Search for DeltaS = 2 nonleptonic hyperon decays.

A sensitive search for the rare decays Omega(-)--> Lambdapi(-) and Xi(0)--> ppi(-) has been performed using data from the 1997 run of the HyperCP (Fermilab E871) experiment. Limits on other such processes do not exclude the possibility of observable rates for |DeltaS| = 2 nonleptonic hyperon decays, provided the decays occur through parity-odd operators. We obtain the branching-fraction limits B(Omega(-)-->Lambdapi(-)) < 2.9 x 10(-6) and B(Xi(0)--> ppi(-)) < 8.2 x 10(-6), both at 90% confidence level.

Journal Article↗

PubMed2005

The TIGR Gene Indices: clustering and assembling EST and known genes and integration with eukaryotic genomes.

Although the list of completed genome sequencing projects has expanded rapidly, sequencing and analysis of expressed sequence tags (ESTs) remain a primary tool for discovery of novel genes in many eukaryotes and a key element in genome annotation. The TIGR Gene Indices (http://www.tigr.org/tdb/tgi) are a collection of 77 species-specific databases that use a highly refined protocol to analyze gene and EST sequences in an attempt to identify and characterize expressed transcripts and to present them on the Web in a user-friendly, consistent fashion. A Gene Index database is constructed for each selected organism by first clustering, then assembling EST and annotated cDNA and gene sequences from GenBank. This process produces a set of unique, high-fidelity virtual transcripts, or tentative consensus (TC) sequences. The TC sequences can be used to provide putative genes with functional annotation, to link the transcripts to genetic and physical maps, to provide links to orthologous and paralogous genes, and as a resource for comparative and functional genomic analysis.

Animals↗

PubMed2005

Increasing central adiposity: the Nepean longitudinal study of young people aged 7-8 to 12-13 y.

BACKGROUND: Estimates of the prevalence of overweight and obesity in young people are typically based on body mass index (BMI). However, BMI may not indicate the level of central adiposity. Waist circumference has therefore been recommended to identify young people at risk of morbidity associated with central adiposity. OBJECTIVE: To investigate (a) change in total and central adiposity between 7-8 and 12-13 y (b) agreement between classifying young people as overweight or obese based on total adiposity and central adiposity, and (c) risk factors associated with the development of total and central adiposity. DESIGN: Anthropometric measurements were taken on 342 children in 1996/97 and 5 y later. Risk factors examined included birth weight, physical activity, TV viewing, pubertal status, parental adiposity, diet and socio-economic status. RESULTS: Between 7-8 and 12-13 y indices of central adiposity increased more than total adiposity; waist circumference z-score increased by (mean+/-s.d.) 0.74+/-0.92 and BMI z-score increased by 0.18+/-0.67. At 12-13 y there was moderate agreement between the two measures of adiposity (weighted kappa=0.64). However, waist circumference identified a greater number of young people as overweight or obese compared to BMI (41.2 vs 29.3%, P<0.001). Adiposity status at 7-8 y, maternal obesity, and pubertal stage were the strongest predictors of BMI status at 12-13 y. Risk factors associated with increased central adiposity were similar. CONCLUSIONS: Overweight and obesity, as measured by waist circumference, is a bigger problem than is currently assessed by BMI. Targeting known risk factors for total adiposity may be an appropriate strategy for preventing increased central adiposity.

Adiposity↗

PubMed2005

Mitoxantrone induces cell death in peripheral blood leucocytes of multiple sclerosis patients.

Mitoxantrone (MX) is a cytotoxic drug with proven clinical efficacy in active multiple sclerosis (MS). In this ex vivo study we investigated the immunological effects of MX on peripheral blood leucocytes (PBL) from MS patients. PBL were isolated from 46 patients with active MS (mean age 42 years, female : male 1.4 : 1) before and immediately after 1 h MX infusion. Isolated PBL were cultured and stimulated with phytohaemagglutinin (PHA), T cell receptor stimulating monoclonal antibody (MoAb) X35 or kept in culture medium alone. Proliferation was measured by [3H]-thymidine incorporation. MX-uptake and cell death in PBL subpopulations was analysed by flow cytometry using antibodies against cluster of differentiation (CD)-surface antigens, annexin V (AnnV) and propidium iodide (PI). MX was incorporated rapidly into PBL. After only a 1-h in vivo exposure, MX reduced proliferative responses in unstimulated and stimulated PBL (PHA: - 17%, MoAb X35: -13%). MX-exposed PBL showed an increase of AnnV+/PI+ cells (unstimulated: 12%, PHA: 15%), which was even more pronounced 2 weeks after infusion. No difference was observed between de novo MX-treated patients and those on long-term MX treatment. In T cell receptor stimulated PBL, cell death was induced preferentially in CD19-positive B cells and to a lesser extent in CD8-positive T cells. MX is incorporated rapidly in circulating PBL of MS patients and induces a pronounced suppression of proliferative responses. This suppression appears to be mediated at least partly by the induction of late apoptotic/necrotic cell death with a preferential susceptibility of B cells.

Adult↗

PubMed2005

A South Australian population-based study of congenital talipes equinovarus.

The aims of this study were to provide a population-based prevalence for congenital talipes equinovarus (CTEV), to conduct an epidemiological investigation into the risk factors for CTEV and describe associated features. The study used a retrospective case-control design of CTEV notified to the South Australian Birth Defects Register between 1986 and 1996 inclusive, linking characteristics of mother and baby from the perinatal data collection. The prevalence of isolated CTEV was 1.1/1000 total births (n = 231). Four factors were significantly associated with an increased risk of CTEV: maternal Aboriginal race (ORadj = 2.0; 95% CI 1.1, 3.6), male gender (ORadj = 2.4; 95% CI 1.8, 3.2), maternal anaemia (ORadj = 1.8; 95% CI 1.0, 2.9) and maternal hyperemesis (ORadj = 3.6; 95% CI 1.3, 9.8). The prevalence of CTEV associated with another birth defect or syndrome (n = 157) was 0.7/1000 total births. CTEV was associated with specific birth defects and also with oligohydramnios when another birth defect was present.

Anemia↗

PubMed2004

Search for CP violation in charged-Xi and Lambda hyperon decays.

We have compared the p and p angular distributions in 117 x 10(6) Xi- -->Lambdapi- -->ppi-pi- and 41 x 10(6) Xi+ -->Lambda pi+ -->p pi+pi+ decays using a subset of the data from the HyperCP experiment (E871) at Fermilab. We find no evidence of CP violation, with the direct-CP-violating parameter AXiLambda identical with (alphaXialphaLambda-alpha Xialpha Lambda)/(alphaXialphaLambda+alphaXialphaLambda)=[0.0+/-5.1(stat)+/-4.4(syst)] x 10(-4).

Journal Article↗

PubMed2004

The protective effect of hypoxic preconditioning on cortical neuronal cultures is associated with increases in the activity of several antioxidant enzymes.

Preconditioning describes a variety of treatments that induce neurons to become more resistant to a subsequent ischemic insult. How preconditioned neurons adapt to subsequent ischemic stress is not fully understood, but is likely to involve multiple protective mechanisms. We hypothesized hypoxic preconditioning induces protection by a coordinated up-regulation of antioxidant enzyme activity. To test this hypothesis, we developed two in vitro models of ischemia/reperfusion, involving oxygen-glucose deprivation (OGD) where neuronal cell death was predominantly by necrosis (necrotic model) or programmed cell death (PCD model). Hypoxic preconditioning 24 h prior to OGD significantly reduced cell death from 83% to 22% in the necrotic model and 68% to 11% in the PCD model. Consistent with the hypothesis, the activity of the antioxidant enzymes glutathione peroxidase, glutathione reductase, and Mn superoxide dismutase were significantly increased by 54%, 73% and 32%, respectively, in neuronal cultures subjected to hypoxic preconditioning. Furthermore, superoxide and hydrogen peroxide concentrations following OGD were significantly lower in the PCD model that had been subjected to hypoxic preconditioning.

Animals↗

PubMed2004

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

PURPOSE: To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). RESULTS: All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). CONCLUSION: There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

Adrenal Cortex Hormones↗