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Biomedical subjects

S Wong

Publications and source records attributed to S Wong.

At least 37 records · Page 2Linked to original sources

Aspirin resistance in cardiovascular disease: a review.

BACKGROUND: Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept of aspirin resistance have led to critical reappraisal of current treatment. This review aims to clarify the evidence for aspirin resistance in patients with atherosclerosis. METHODS: Medline search was performed to identify publications concerned with antiplatelet effects of aspirin and failure of aspirin therapy. Manual cross referencing was also performed. RESULTS AND CONCLUSION: Wide variations in the rate of aspirin resistance (5.5-75%) have been reported. The lack of consensus on an appropriate definition and the number of different tests used to investigate aspirin resistance needs to be addressed. There are few studies where the primary aim was to document aspirin resistance or aspirin non-response. Further work should aim to investigate if aspirin resistance is clinically important and, if it is, what treatments may be beneficial to the at risk patient.

Arteriosclerosis↗

Five years managing metastatic non-small cell lung cancer: experience at a teaching hospital.

BACKGROUND: The management of patients with metastatic non-small cell lung cancer (NSCLC) is complex. Some studies have demonstrated that the care of patients with NSCLC may be suboptimal. AIM: To review the management of patients with metastatic NSCLC treated at a single teaching hospital over a 5-year period. METHOD: All patients with metastatic NSCLC treated at a single teaching hospital over a 5-year period (1998-2002) were identified. Data were collected by a retrospective record review. RESULTS: Of 343 patients with metastatic NSCLC, 157 patients were deemed eligible for this review. Thirty-one patients (19%) were admitted to the Medical Oncology Unit at initial presentation. Twenty-four patients (15%) were not referred to either the Medical Oncology Unit or the Palliative Care Unit. Forty-four patients (28%) received chemotherapy, six of whom (14%) were enrolled onto a clinical trial. Six separate chemotherapy regimens were used. The median survival was 5 months and the 1-year survival rate was 19.8%. CONCLUSIONS: The present audit demonstrates some shortfalls in the optimal clinical care of patients with metastatic NSCLC at a large teaching hospital. The main selection criteria of consideration for chemotherapy are age, performance status and presence of symptoms. A subset of patients was not referred to either the Medical Oncology Unit or the Palliative Care Unit and consistency in the choice of chemotherapy was lacking. Survival data and the rate of patients entered onto clinical trials are acceptable; however, further improvements can be made by the institution of multidisciplinary clinics and the education of referring clinicians.

Adult↗

Genetically decreased CYP2A6 and the risk of tobacco dependence: a prospective study of novice smokers.

OBJECTIVE: Case control studies in adults suggest that defective alleles in the gene that codes for the hepatic cytochrome P450 2A6 (CYP2A6) protect against nicotine dependence (ND) and higher levels of cigarette consumption. These two hypotheses were tested in young adolescents. DESIGN: Self reports of tobacco use and ND symptoms were collected every 3-4 months in a prospective study of 1293 grade 7 students from a convenience sample of 10 schools. SUBJECTS: 281 smokers with genetic data were analysed; those who were not already tobacco dependent and who had inhaled (n = 228) were followed 29.9 months on average, until they became dependent or were censored. MAIN OUTCOME MEASURES: The association between metabolic activity, represented by CYP2A6 genotype, and conversion to dependence was analysed using Cox's proportional hazards model. RESULTS: During follow up 67 subjects (29.4%) became dependent. Relative to CYP2A6*1/*1, having 1-2 copies of the inactive CYP2A6*2 or *4 variant was a strong risk factor for developing dependence (hazard ratio 2.8, 95% confidence 1.3 to 6.3). Subjects with 1-2 partially inactive CYP2A6*9 or *12 variants were not at increased risk. Mean past-week cigarette consumption at the end of follow up (controlling for age, sex, and number of months since first inhalation) among dependent subjects was 29.1 among normal inactivators, compared to 17.2, and 12.7 among slower (1-2 copies of *9 or *12), and slowest (1-2 copies of *2 or *4) inactivators, respectively (p = 0.09). CONCLUSION: Adolescents with 1-2 copies of CYP2A6*2 or *4 are at substantially increased risk of becoming dependent but smoke less once dependent. Genetic risk for ND may need to be considered in the conceptualisation of tobacco control programmes for adolescents.

Adolescent↗

PPAR-gamma agonists as therapy for diseases involving airway neutrophilia.

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear hormone receptors belonging to the steroid receptor super-family. Previously, the present authors have shown that PPAR-gamma agonists inhibit the release of inflammatory cell survival factors and induce apoptosis in vitro. The aim of this study was to determine the effect of two structurally different PPAR agonists in an in vivo model of lipopolysaccharide (LPS)-induced airway inflammation. Mice were treated with PPAR agonists, rosiglitazone or SB 219994, prior to exposure to aerosolised LPS, and the extent of airway inflammation was assessed 3 h later. In these experiments, the PPAR ligands inhibited LPS-induced airway neutrophilia and associated chemoattractants/survival factors (keratinocyte-derived chemokine and granulocyte-colony stimulating factor) in the mouse lung. The present authors postulate that if a peroxisome proliferator-activated receptor agonist has the same effect in man, and neutrophils are important in the progression of respiratory diseases, such as chronic obstructive pulmonary disease, then this class of compounds could be a potential therapy. Furthermore, several peroxisome proliferator-activated receptor-gamma agonists have been shown to be clinically effective for the treatment of type II diabetes, suggesting that any benefit of peroxisome proliferator-activated receptor-gamma ligands in the progression of respiratory diseases, which may involve airway neutrophilia, could be explored relatively quickly.

Administration, Oral↗

The effects of sustained exercise and hypoxia upon oxygen tensions in the red muscle of rainbow trout.

Teleost fish possess discrete blocks of oxidative red muscle (RM) and glycolytic white muscle, whereas tetrapod skeletal muscles are mixed oxidative/glycolytic. It has been suggested that the anatomy of RM in teleost fish could lead to higher intramuscular O2 partial pressures (PO2) than in mammalian skeletal muscles. This study provides the first direct experimental support for this suggestion by using novel optical fibre sensors to discover a mean (+/- S.E.M., N=6) normoxic steady-state red muscle PO2 (PrmO2) of 61+/-10 mmHg (1 mmHg=133.3 Pa) in free-swimming rainbow trout Oncorhynchus mykiss. This is significantly higher than literature reports for mammalian muscles, where the PO2 never exceeds 40 mmHg. Aerobic RM powers sustained swimming in rainbow trout. During graded incremental exercise, PrmO2 declined from 62+/-5 mmHg at the lowest swim speed down to 45+/-3 mmHg at maximum rates of aerobic work, but then rose again to 51+/-5 mmHg at exhaustion. These measurements of PrmO2 during exercise indicated, therefore, that O2 supply to the RM was not a major limiting factor at exhaustion in trout. The current study found no evidence that teleost haemoglobins with a Root effect cause extremely elevated O2 tensions in aerobic tissues. Under normoxic conditions, PrmO2 was significantly lower than arterial PO2 (119+/-5 mmHg), and remained lower when the arterial to tissue PO2 gradient was reduced by exposure to mild hypoxia. When two sequential levels of mild hypoxia (30 min at a water PO2 of 100 mmHg then 30 min at 75 mmHg) caused PaO2 to fall to 84+/-2 mmHg then 61+/-3 mmHg, respectively, this elicited simultaneous reductions in PrmO2,to 51+/-6 mmHg then 41+/-5 mmHg, respectively. Although these hypoxic reductions in PrmO2 were significantly smaller than those in PaO2, the effect could be attributed to the sigmoid shape of the trout haemoglobin-O2 dissociation curve.

Analysis of Variance↗

Open mesh repair of incisional hernias with significant loss of domain.

BACKGROUND: Incisional hernias develop in up to 13% of laparotomy incisions: the most difficult to repair are complex, multiply recurrent hernias with significant loss of domain (>15-20% of the abdominal contents). METHODS: Retrospective analysis by standard proforma of a series of 52 patients operated on at a single institution between 1996 and 2002. All patients received pre-operative CT and anaesthetic assessment. Patients with significant tissue loss were assessed by a plastic surgeon. Cardiorespiratory status was optimised and trophic skin ulcers treated before operation. RESULTS: Sublay repair was applied in 33 patients, onlay in 16 patients, one patient received inlay repair and two patients the Ramirez abdominoplasty. Additional procedures of stoma closure, muscle flap or abdominoplasty were carried out in 7 patients. Complications occurred in 18 (34.6%) patients, 5 of whom required further surgery for haematoma, infection or fistulisation. One patient died from pulmonary embolism after postoperative complications. Three recurrences were apparent after follow-up of 6 months to 6 years. CONCLUSIONS: Complex incisional hernias are a challenging surgical problem. Careful patient selection and surgical technique with a team involving anaesthetists and plastic surgeons is required. Post-operative management may require facilities in HDU and ITU. Clinical trials are required to identify techniques and materials which give the best results.

Adult↗

Larval anisakid infections of some tropical fish species from north-west Australia.

Despite the commercial and zoonotic importance of larval anisakid infestations of teleosts, their distribution among Australia's diverse marine fish fauna is poorly understood. A preliminary survey of Australia's tropical north-west revealed a generally high prevalence of larval anisakids representing four genera (Anisakis, Terranova, Thynnascaris and Raphidascaris) among only seven fish species. The potential impact of high larval anisakid infections on both the health of recreational fishermen and aquaculture environments is discussed.

Animals↗

Molecular characterization of bovine enteric caliciviruses: a distinct third genogroup of noroviruses (Norwalk-like viruses) unlikely to be of risk to humans.

Bovine enteric caliciviruses (BoCVs) have been classified in the Norovirus (Norwalk-like virus) genus of the Caliciviridae, raising questions about zoonotic transmission and an animal reservoir for the human Norwalk-like viruses (NLVs), an important cause of nonbacterial gastroenteritis in humans. We examined the genetic relationship of human NLVs to BoCVs that were identified by using reverse transcription-PCR with primer pairs originally designed to detect human NLVs. Polymerase, capsid, and open reading frame 3 (ORF3) gene sequence analyses of BoCVs that were identified from 1976 to 2000 from throughout the United Kingdom showed that BoCVs formed a distinct third genogroup of closely related viruses distinct from the human genogroup I and II NLVs. Evidence was not obtained to support the concept that BoCVs are circulating in humans and pose a threat to human health.

Amino Acid Sequence↗

Fractionation of natural organic matter in drinking water and characterization by 13C cross-polarization magic-angle spinning NMR spectroscopy and size exclusion chromatography.

Natural organic matter from drinking water sources was fractionated, and the fractions were characterized by NMR and SEC with the aim of relating NOM structure to treatability. Organic matter was isolated from two Australian surface waters (Horsham, Moorabool) by reverse osmosis and from a groundwater (Wanneroo) by anion exchange. The isolates were fractionated according to polarity and charge by resin adsorption. 13C NMR spectra of the freeze-dried fractions showed the most hydrophobic fraction to be high in aliphatic and aromatic carbon while slightly hydrophobic organics have more carbonyl and alkoxyl carbon. The Horsham and Wanneroo hydrophilic fractions show strong alkoxyl signals attributed to carbohydrate. Moorabool hydrophilics contain aromatic (phenolic) carbon; the apparent absence of carbohydrate appears to be an artifact. Size-exclusion chromatograms were recorded on the original and fractionated organics with both UV and dissolved organic carbon detection. The Horsham and Moorabool organics have similar molecular size distributions while Wanneroo is dominated by strongly absorbing species having large hydrodynamic radii. The hydrophobic and charged hydrophilic fractions also have high apparent MW, while the neutral fraction is higher in low-MW compounds of relatively low specific absorbance, suggestive of carbohydrates.

Carbohydrates↗

Messenger RNA for progesterone receptor isoforms in the late-gestation rat uterus.

The progesterone receptor (PR) has three isoforms, PR-A, PR-B, and PR-C, which have different physiological effects. PR-A may inhibit PR-B-mediated transcription. Parturition requires withdrawal of progesterone (P4). This could occur through decreased P4 concentrations and/or a change in PR isoforms to diminish the effect of P4. We measured mRNA for PR isoforms in rat uterine tissues through late gestation and investigated the effects of antagonists to estrogen (tamoxifen) and P4 (RU-486). Two specific probes were used for ribonuclease protection assays; one (PR-total) measured PR-A, PR-B, and PR-C, and the other recognized only PR-B. PR-total mRNA increased significantly through late gestation, whereas PR-B was unchanged. The ratio of PR-total to PR-B peaked on the day before parturition. Tamoxifen delayed parturition and inhibited the increase in PR-total without affecting PR-B mRNA. RU-486 caused early parturition associated with increased PR-total mRNA, with no change in PR-B. We conclude that there are significant changes in PR isoforms in late-gestation rat uterus. These changes may be regulated by estrogen and P4 and may influence the timing of parturition.

Animals↗

Generation of a life-expanded rhesus monkey fibroblast cell line for the growth of rhesus rhadinovirus (RRV).

RRV, the rhesus macaque equivalent to HHV-8 or kaposi's sarcoma-associated herpesvirus (KSHV) was recently isolated from a simian immunodeficiency virus (SIV) infected macaque with a lymphoproliferative disorder. The growth of RRV in tissue culture requires propagation of primary rhesus monkey fibroblasts (RFs). In an effort to extend the life of these primary cells in tissue culture, the catalytic subunit of telomerase (hTERT) was introduced into RF cells using a recombinant retrovirus. This new cell line, Telo-RFs, have currently been passed in tissue culture over 80 times compared to a maximum passage number of 38 for wild type RFs, remain fully permissive for RRV DNA replication and production of infectious virus. Viral gene expression of immediate-early and early RNA transcripts was virtually identical to that observed in wild-type (wt) RFs. In addition, transfection experiments show that telo-RFs are easily and more efficiently transfected than wtRFs.

Animals↗

Ammonia threshold--comparison to lactate threshold, correlation to other physiological parameters and response to training.

During standard graded exercise, blood lactate and blood ammonia levels increase in parallel and the two thresholds appear at the same relative intensity. The first part of this study aimed at comparing ammonia threshold to lactate threshold with five different graded exercise protocols. A significant difference between the two thresholds was found only in the continuous protocol with 4-min steps in which ammonia threshold appeared at a higher intensity than lactate threshold. The second part of the study investigated the correlation of ammonia threshold to some common physiological measurements. Correlation was significant with lactate threshold, ventilation threshold and endurance time. No correlation was found the anaerobic power, anaerobic capacity measurement and peak VO2. Ammonia threshold was also studied before and after endurance training and sprint training. The 8-week endurance training program was able to delay the appearance of ammonia threshold, but not the 8-week sprint training program. Findings in this study demonstrate that ammonia threshold is a physiological parameter that should be recognized and has potential to be applied for the evaluation of exercise capacity and the effectiveness of endurance training programs.

Adult↗

Use of electrolysis as an adjunct to liver resection.

BACKGROUND: Patients with hepatic metastases are potentially curable if all the diseased tissue can be resected. Unfortunately, only 10-20 per cent of patients are suitable for curative resection. Electrolysis is a novel non-thermal method of tissue ablation. When used in conjunction with surgery it may increase the number of resectable liver tumours with curative treatment. METHODS: All patients had been deemed inoperable using currently accepted criteria. Nine patients with hepatic deposits from colorectal carcinoma underwent combined surgical resection and electrolytic ablation of metastases. RESULTS: The treatment was associated with minimal morbidity. Within the electrolytically treated area seven patients had no radiological evidence of recurrence at a median follow-up of 9 (range 6-43) months; local recurrence was detected in two patients. Six of the nine patients had metastases elsewhere in the liver with four having extrahepatic metastases. Three patients remain tumour free. Three patients died. The median survival was 17 (range 9-24) months from the time of treatment. DISCUSSION: Electrolysis with resection may confer a disease-free and overall survival benefit. The small size of this initial study precludes statistical analysis, but preliminary results are encouraging.

Adult↗

Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study.

OBJECTIVE: To investigate patients' adherence to statin treatment prescribed following their first myocardial infarction (MI) and to estimate the effect of adherence to statins on recurrence of MI and all cause mortality. DESIGN: Cohort study using a record linkage database. SETTING: Tayside, Scotland, UK. PATIENTS: Patients who experienced their first MI between January 1990 and November 1995. MAIN OUTCOME MEASURES: Percentage of statin use and adherence to statins by patients after an MI and the relative risk of hospitalisation for recurrent MI. The effect of adherence on all cause mortality was also examined. The covariates used were age, sex, socioeconomic deprivation, serum cholesterol concentration, diabetes mellitus, cardiovascular drug use, and other hospitalisations. RESULTS: Of 5590 patients who experienced an incident MI, 717 (12.8%) experienced at least one further MI. Only 7.7% of patients used statins after an MI during the study period. Compared with those not taking statins, those who had 80% or better adherence to statin treatment had an adjusted relative risk of recurrent MI of 0.19 (95% confidence interval (CI) 0.08 to 0.47) and all cause mortality of 0.47 (95% CI 0.22 to 0.99). There was no significant reduction in either end point for those who were less than 80% adherent to statins. CONCLUSIONS: Despite the infrequent use of statin during the study period, good adherence to statin treatment was associated with lower risk of recurrent MI.

Adult↗

In vivo hippocampal glucose metabolism in mesial temporal lobe epilepsy.

BACKGROUND: The appearance of decreased 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake in the mesial temporal region in temporal lobe epilepsy may simply reflect loss of gray matter due to hippocampal atrophy. Increased partial volume effects due to atrophic hippocampi may further increase appearance of hypometabolism. METHODS: The authors used a combination of MRI-PET coregistration, with MRI-based gray matter segmentation, and partial volume correction to improve the examination of hippocampal specific glucose uptake in FDG PET. The goal was to determine 1) if relative mesial temporal hypometabolism is an artifact of gray matter (hippocampal) atrophy, 2) whether hippocampal metabolism correlates with atrophy evaluated on MRI, and 3) if MRI-based partial volume correction influences measurement of hippocampal metabolic-volume relationships, including epilepsy lateralization. RESULTS: Findings showed that ipsilateral hippocampi of mesial temporal lobe epilepsy (MTLE) are relatively hypometabolic per unit of gray matter volume, and that hippocampal metabolism directly correlates with hippocampal volume. Specifically, partial volume corrected hippocampal metabolism correlated strongly (r = 0.613, p < 0.001) with hippocampal volume. Without partial volume correction, a weaker, but still significant, correlation was present (r = 0.482, p < 0.001). Degree of asymmetry was consistently greater and provided higher sensitivity of lateralization with partial volume vs non-partial volume corrected metabolic measurements. CONCLUSIONS: Although, decreased metabolism may occur in the absence of neuronal cell loss, hippocampal atrophy and presumed degree of neuronal cell loss appears to be a primary factor involved in the cause of decreased metabolism in epileptogenic hippocampi. Partial volume correction is recommended for optimal interpretation of hippocampal structure and function relationships.

Adolescent↗

Modeling Philadelphia chromosome positive leukemias.

The Ph chromosome has been genetically linked to CML and ALL. Its chimeric fusion gene product, BCR-ABL, can generate leukemia in mice. This review will discuss selected model systems developed to study BCR-ABL induced leukemia and focuses on what we have learned about the human disease from these models. Five main experimental approaches will be discussed including: (i) Reconstitution of mice with bone marrow cells retrovirally transduced with BCR-ABL; (ii) Transgenic mice expressing BCR-ABL; (iii) Knock-in mice with BCR-ABL expression driven from the endogenous bcr locus; (iv) Development of CML-like disease in mice with loss of function mutations in heterologous genes; and (v) ES in vitro hematopoietic differentiation coupled with regulated BCR-ABL expression.

Animals↗