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Biomedical subjects

C Chan

Publications and source records attributed to C Chan.

At least 19 recordsLinked to original sources

Assessing the evidence for an association between circumferential tumour clearance and local recurrence after resection of rectal cancer.

OBJECTIVE: Circumferential resection margin involvement (CRMI) after resection of rectal cancer is regarded as a risk factor for local recurrence. We have been able to identify only nine peer-reviewed English-language publications which focus primarily on this association, and they report widely differing rates of local recurrence. The aims of this study were to review possible reasons for this variability and to assess the evidence for the micrometrically measured threshold defining CRMI. METHOD: Methodological and statistical evaluation of relevant literature. RESULTS: Several factors which could account for this variability are discussed including the nature of the patient series, surgical technique, curative vs palliative resections, pathology technique, the definition of CRMI, adjuvant therapy, tumour stage, definition and ascertainment of local recurrence, length of follow-up and method of analysis. The objective evidence for the conventional definition of CRMI as tumour 1 mm or less from a circumferential margin is considered along with the evidence supporting a recent proposal that the margin be extended to 2 mm or less. The evidence is numerically weak in both cases and we believe that neither definition should be set in concrete at this stage. CONCLUSION: Pending further research, we recommend that routine pathology reports should record frank tumour transection, if present, or otherwise report the histological width of the margin between the tumour and the nearest circumferential line of resection in millimetres. The definition of CRMI should be simply histological evidence of tumour in a line of resection, that is, a margin of 0 mm. The definition of CRMI as a margin of <or=1 mm should not be adopted as a basis for assessing the quality of surgery.

Humans↗

Risk factors for tumour present in a circumferential line of resection after excision of rectal cancer.

BACKGROUND: Transected tumour in a circumferential line of resection after excision of rectal cancer carries a high likelihood of local recurrence. The aim of this study was to identify independent risk factors for transected tumour and to examine their temporal variability. METHODS: Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1971 to July 2004. Transected tumour was defined as tumour present histologically in a line of resection and was assessed in all specimens. RESULTS: Transection occurred in 129 of 1613 patients (8.0 (95 per cent confidence interval 6.7 to 9.4) per cent). The following variables were independently associated with transected tumour: tumour perforation, a non-restorative operation, tumour adherence, non-standardized operative technique, preoperative radiotherapy, male sex, histological involvement of an adjacent organ or tissue, high-grade tumour and venous invasion. The mean number of risk factors per patient per year and the annual percentage of patients with transection varied distinctly over the history of the database. CONCLUSION: The varying prevalence of risk factors, both within and between hospitals and patient series, should be taken into account if the rate of transection is to be regarded as an index of the quality of surgery.

Aged↗

The evolving role of gene-based treatment in surgery.

BACKGROUND: The completion of the sequencing of the human genome in 2003 marked the dawn of a new era of human biology and medicine. Although these remarkable scientific advances improve the understanding of human biology, the question remains how this rapidly expanding knowledge of functional genomics affects the role of surgeons. This article reviews the potential therapeutic application of gene therapy for various surgical conditions. METHODS: The core of this review was derived from a Medline database literature search. RESULTS AND CONCLUSION: The currently available vectors in the field of gene therapy and their limitations for clinical applications were analysed. The achievements of gene therapy in clinical trials and the future ramifications for surgery were also explored. Whether gene therapy takes a major role in surgical practice will depend greatly on the success of future vector development. Advances in viral vector technology to reduce the inflammatory effect, and improvements in the efficiency of gene delivery using non-viral vector technology, would allow this form of therapy to become more clinically applicable.

Drug Resistance↗

Delay in diagnosis and its effect on outcome in head and neck cancer.

We examined the records of two cohorts of patients who were seen from 1960 to 1999 with a diagnosis of squamous cell carcinoma (SCC) of the mouth and throat, one series being retrospective (n=400) and the other prospective (n=213) to find out about delays in diagnosis. The median delay in both cohorts was 3 months and the patients were responsible for the delay in most cases (n=319, 81% and n=160, 78%, respectively). Half the patients in each cohort had delayed diagnoses (n=217, 54% and n=119, 56%, respectively) and similar percentages (n=110, 53% and n=172, 47%) presented with advanced disease (stage III or IV). These were not the same patients for there was no correlation between delay and stage or survival. Logistic regression analysis showed that non-white race (p=0.01) and high-grade histology (p=0.002) predicted advanced disease. The proportion of patients presenting with advanced disease had not changed in 40 years despite public education. We suggest that some tumours may be silent and that initial symptoms do not reliably predict early disease.

Adolescent↗

Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery.

BACKGROUND: This observational study sought to determine whether the degree of hemodilution during cardiopulmonary bypass is independently related to perioperative acute renal failure necessitating dialysis support. METHODS: Data were prospectively collected on consecutive patients undergoing cardiac operations with cardiopulmonary bypass from 1999 to 2003 at a tertiary care hospital. The independent relationship was assessed between the degree of hemodilution during cardiopulmonary bypass, as measured by nadir hematocrit concentration, and acute renal failure necessitating dialysis support. Multivariate logistic regression was used to control for variables known to be associated with perioperative renal failure and anemia. RESULTS: Of the 9080 patients included in the analysis, 1.5% (n = 134) had acute renal failure necessitating dialysis support. There was an independent, nonlinear relationship between nadir hematocrit concentration during cardiopulmonary bypass and acute renal failure necessitating dialysis support. Moderate hemodilution (nadir hematocrit concentration, 21%-25%) was associated with the lowest risk of acute renal failure necessitating dialysis support; the risk increased as nadir hematocrit concentration deviated from this range in either direction (P = .005). Compared with moderate hemodilution, the adjusted odds ratio for acute renal failure necessitating dialysis support with severe hemodilution (nadir hematocrit concentration <21%) was 2.34 (95% confidence interval, 1.47-3.71), and for mild hemodilution (nadir hematocrit concentration >25%) it was 1.88 (95% confidence interval, 1.02-3.46). CONCLUSIONS: Given that there is an independent association between the degree of hemodilution during cardiopulmonary bypass and perioperative acute renal failure necessitating dialysis support, patient outcomes may be improved if the nadir hematocrit concentration during cardiopulmonary bypass is kept within the identified optimal range. Randomized clinical trials, however, are needed to determine whether this is a cause-effect relationship or simply an association.

Acute Kidney Injury↗

Australian consumers are sceptical about but influenced by claims about fat on food labels.

OBJECTIVES: To explore the beliefs and attitudes of Australian consumers to claims about fat made on the labels of packaged food. DESIGN: Content analysis of transcripts from focus group discussions. SUBJECTS: A total of 26 female and 10 male participants aged 20-80 y, recruited by advertisement into six focus groups, stratified by age, sex and health status. RESULTS: Awareness of claims about fat was high in this sample of Australians and participants admitted that they influenced their purchase decisions. The most preferred form of claim was 'X% fat free'. Claims were considered most useful on foods that were high in fat. There was considerable scepticism about all nutrient claims, and consumers preferred to check claims about fat against the values in the nutrition information panel. Many claims were seen as advertising that could be misleading, deceptive or confusing. While claims about fat might prompt product trial, factors such as price, taste, naturalness, as well as other nutritional factors, also influenced purchase decisions. Some consumers believe low fat claims encourage over consumption of foods. CONCLUSIONS: Changes to regulations governing nutrition claims on food labels should be made to enhance their credibility and support their role in assisting consumers to make healthier food choices.

Adult↗

Alginate as an auxiliary bacterial membrane: binding of membrane-active peptides by polysaccharides.

The chronicity of Pseudomonas aeruginosa infections in cystic fibrosis (CF) patients is characterized by overproduction of the exopolysaccharide alginate, in which biofilm bacteria are embedded. Alginate apparently contributes to the antibiotic resistance of bacteria in this form by acting as a diffusion barrier to positively charged antimicrobial agents. We have been investigating cationic antimicrobial peptides (CAPs) (prototypic sequence: KKAAAXAAAAAXAAWAAXAAAKKKK-NH(2), where X is any of the 20 commonly occurring amino acids) that were originally designed as transmembrane mimetic peptides. Peptides of this group above a specific hydrophobicity threshold insert spontaneously into membranes and have antibacterial activity at micromolar concentrations. While investigating the molecular basis of biofilm resistance to peptides, we found that the anionic alginate polysaccharide induces conformational changes in the most hydrophobic of these peptides typically associated with insertion of such peptides into membrane environments [Chan et al., J. Biol. Chem. (2004) vol. 279, pp. 38749-38754]. Through a combination of experiments measuring release of the fluorescent dye calcein from phospholipid vesicles, peptide interactions with vesicles in the presence and absence of alginate, and affinity of peptides for alginate as a function of net peptide core hydrophobicity, we show here that alginate offers a microenvironment that provides a protective mechanism for the encased bacteria by both binding and promoting the self-association of the CAPs. The overall results indicate that hydrophilic alginate polymers contain a significant hydrophobic compartment, and behave as an 'auxiliary membrane' for bacteria, thus identifying a unique protective role for biofilm exopolysaccharide matrices.

Alginates↗

Childhood sleep-disordered breathing and its implications for cardiac and vascular diseases.

OBJECTIVE: To systematically evaluate the recent literature regarding the relationship between childhood sleep-disordered breathing (SDB)/obstructive sleep apnoea (OSA) and cardiovascular diseases in children. METHODS: The literature about SDB/OSA and blood pressure, sympathetic activation, arterial distensibility, ventricular hypertrophy and insulin resistance were studied. Meta-analysis of risk of hypertension and high apnoea-hyponoea index were performed to calculate the combined odds ratio and it is equal to 2.93 (95% CI = 1.18-7.29). RESULTS: The results suggest a significant association between SDB/OSA and hypertension. However, the data are not adequate to draw firm conclusion although evidences were emerging to suggest that SDB/OSA affects blood pressure in either directions in children. Limited evidences also suggest that SDB/OSA is associated with increased sympathetic activation, decreased arterial distensibility and ventricular hypertrophy. CONCLUSIONS: There is now increasing but not adequate evidence that childhood SDB/OSA is associated with detectable cardiovascular abnormalities.

Adolescent↗

Primary care of patients with sexually transmitted diseases or genitourinary symptoms in Hong Kong.

OBJECTIVES: To determine the adequacy of care received from general practitioners by patients with sexually transmitted diseases or genitourinary symptoms. DESIGN: Prospective study. SETTING: Hong Kong. PARTICIPANTS: Diagnoses and drug data obtained from logbooks submitted by doctors studying for the Diploma in Family Medicine and candidates for Fellowship examinations between 1999 and 2002. MAIN OUTCOME MEASURES: Diagnosis or symptom of a sexually transmitted disease and prescribed treatment. RESULTS: Sexually transmitted diseases and genitourinary symptoms accounted for 1.1% of the workload of these community doctors in Hong Kong. The majority of patients were young adult males. The overall standard of treatment was inadequate: both multi-pharmacy and inappropriate treatment was common; in up to 30% of cases, doctors ignored local or international guidelines. CONCLUSION: Primary care doctors play an important role in the diagnosis and management of sexually transmitted diseases or genitourinary symptoms in Hong Kong. A high index of suspicion should be maintained and continuing education made available if doctors are to provide an equally high standard of care.

Adult↗

Motor development of very low birthweight infants with chronic lung disease - a comparative study.

INTRODUCTION: To determine whether chronic lung disease (CLD) influences specific aspects of motor development in infancy. MATERIALS AND METHODS: Twenty-nine very low birthweight infants with CLD at 36 weeks' post-conceptional age and 31 infants without CLD were evaluated at 8 months' and 24 months' corrected age using the Neurosensory Motor Development Assessment. Perinatal and neonatal characteristics of the infants with CLD and control infants were compared using the chi-square test for categorical variables and Student's t-test for continuous variables. The relationship between CLD and adverse outcome was measured by the odds ratio (OR) and its 95% confidence interval (CI). RESULTS: The overall developmental scores of the CLD infants were significantly different compared with control infants at 8 months. By 2 years of age, both groups of infants showed marked improvement in motor performance. However, differences persisted in the area of postural balance and sensory motor skills. Taking periventricular haemorrhage and periventricular leukomalacia into consideration, CLD contributed significantly to the occurrence of motor dysfunction at 8 months of age [odds ratio (OR), 7.4; 95% confidence interval (CI), 2.1 to 26.5]. The impact of CLD on motor development remained substantial, though not statistically significant (OR, 3.7; 95% CI, 0.4 to 37.9) at 2 years of age. CONCLUSION: CLD has a definite effect on motor development. The pathologic influence of CLD on motor development remains speculative but results of this study emphasise the need for careful neurodevelopmental follow-up of infants with CLD, whether or not these infants suffer intraventricular haemorrhage or periventricular leukomalacia.

Bronchopulmonary Dysplasia↗

Major pulmonary embolism treated with a rheolytic thrombectomy catheter.

The current treatment of massive pulmonary embolism (PE) has been either thrombolysis or surgical embolectomy. Recently, percutaneous rheolytic thrombectomy has emerged as an alternative treatment in patients with contraindications to thrombolysis. We describe a 45-year-old woman who developed major PE post-operatively, who was treated successfully with the AngioJet system. The principles of percutaneous rheolytic thrombectomy, its effectiveness and potential complications are discussed.

Angiography↗

Tissue deformation and shape models in image-guided interventions: a discussion paper.

This paper promotes the concept of active models in image-guided interventions. We outline the limitations of the rigid body assumption in image-guided interventions and describe how intraoperative imaging provides a rich source of information on spatial location of anatomical structures and therapy devices, allowing a preoperative plan to be updated during an intervention. Soft tissue deformation and variation from an atlas to a particular individual can both be determined using non-rigid registration. Established methods using free-form deformations have a very large number of degrees of freedom. Three examples of deformable models--motion models, biomechanical models and statistical shape models--are used to illustrate how prior information can be used to restrict the number of degrees of freedom of the registration algorithm and thus provide active models for image-guided interventions. We provide preliminary results from applications for each type of model.

Algorithms↗

Laparoscopic drainage of pancreatic pseudocysts.

BACKGROUND: Laparoscopic drainage of pancreatic pseudocysts (PPs) has been used in selected cases. The aim of this study is to analyze our results with the laparoscopic technique and to compare them with those of a cohort of patients treated by open surgery during the same time period. PATIENTS AND METHODS: Ten patients underwent laparoscopic drainage of PPs during a 7-year period [laparoscopic group (LG)]. The type of drainage was chosen according to the size and location of the PP. Demography, surgical details, results, and complications were analyzed and contrasted with those of 6 patients who underwent open drainage [open group (OG)]. RESULTS: All patients presented with mature PPs developed after a documented episode of acute pancreatitis. Mean age of the LG was 42 years (six males and four females). In the OG, mean age was 36 years (five males and one female). Etiology of the pancreatitis was alcoholic in eight patients, biliary in five, toxic in two, and associated with systemic lupus erythematous in one. Laparoscopic procedures included Roux-en-Y cystojejunostomy in four patients, extraluminal cystogastrostomy in four, and intraluminal cystogastrostomy in two. There were no conversions. In the OG, cystogastrostomy was performed in three patients and Roux-en-Y cystojejunostomy in three. One patient in the LG developed upper gastrointestinal bleeding the day after surgery that resolved uneventfully, one patient presented a postoperative abscess that required open drainage, and one patient presented a residual pseudocyst that was treated by endoscopy. Morbidity in the OG included a small bowel obstruction secondary to an internal hernia that required reoperation, pneumonia, and a residual pseudocyst that was treated conservatively in one patient each. At a median follow-up of 22 months (range, 1-72) all patients were asymptomatic with no evidence of recurrent disease by computed tomography scan. CONCLUSION: Laparoscopic drainage of PPs is feasible, safe, and effective. Results are similar to those obtained using the open technique.

Adolescent↗

Antibody response to the human stress protein BiP in rheumatoid arthritis.

OBJECTIVES: The human stress protein BiP (immunoglobulin binding protein) has been implicated in the pathogenesis of rheumatoid arthritis (RA) since BiP was found to stimulate synovial T-cell proliferation and anti-BiP antibodies are present in the serum of RA patients. The aim of this study was the development of a rapid and reproducible enzyme-linked immunosorbent assay (ELISA) to determine the specificity and sensitivity of anti-BiP antibodies in RA. METHODS: An ELISA was developed that detected antibodies to BiP. The prevalence of anti-BiP antibodies was determined in sera from patients with early and established RA, sera antedating the onset of RA and sera from patients with other inflammatory and autoimmune diseases and healthy controls. RESULTS: We have confirmed the increased prevalence of antibodies to BiP in the sera of a large cohort of patients with established RA (specificity 71% and sensitivity 73%) and early RA (specificity 65% and sensitivity 66%). In pre-disease sera, median 2.5 yr (interquartile range 1.1-4.7) before symptoms of joint disease, the sensitivity for anti-BiP antibodies was 45% and the specificity was 65% for the development of RA. CONCLUSION: Antibodies to BiP are found in the sera of patients with RA and in sera antedating the onset of RA.

Adult↗

Phenotypic and functional differences between human saphenous vein (HSVEC) and umbilical vein (HUVEC) endothelial cells.

The vascular endothelial cell (EC) plays an essential role in the pathogenesis of inflammation, transplant rejection and tumour metastasis. Most research on vascular ECs uses human umbilical vein endothelial cells (HUVECs). However, HUVECs are derived from immune-naive foetal tissue, and show significant functional differences from adult vascular endothelium. In this paper, we characterise an alternative model based on human saphenous vein ECs (HSVECs), describe their culture conditions and provide a detailed functional comparison with HUVECs. Compared with HUVECs, HSVECs show an increased sensitivity to ox-LDL and a reduced response to cytokines, as indicated by adhesion molecule expression as well as leukocyte adhesion and transmigration. With respect to their ability to present antigen, HSVECs have a higher level of HLA-DR, CD40 and ICOS-L following cytokine stimulation. In addition, HSVECs upregulate the costimulatory ligand CD80 (B7.1) following CD40 ligation, and support allogeneic T cell proliferation, while HUVECs fail to express CD80. Due to differential expression of adhesion molecules, poorly differentiated tumour cell lines also showed more adhesion to HSVECs than to HUVECs. These results indicate that HSVECs have advantages over HUVECs for studying adult vascular endothelial pathology in vitro.

Base Sequence↗

Tolerance mechanisms and recent progress.

There has been tremendous progress in our understanding of the mechanisms mediating allograft tolerance, which have been revealed to be far more complex and regulated than hitherto suspected. New results have enriched our understanding of the relative contributions of the direct and indirect pathways to immunity and tolerance over time. The role of central tolerance has been expanded with the surprising discovery of "ectopic" or "promiscuous" antigens expressed by medullary thymic epithelial cells, and the function of the thymus in generating naturally occurring CD4+ CD25+ regulatory T cells. In the periphery, it is increasingly appreciated that tolerance is a highly active process, with tolerogenic dendritic cells and regulatory T cells being the major players. However, the challenge of understanding the complex interactions regulating the dynamic balance between immunity and tolerance are formidable, and new tools from the more formal disciplines of nonlinear dynamics and systems engineering may help provide insight. Although many hurdles remain, the progress in elucidating the basic mechanisms of tolerance is rapidly being translated into clinical trials and provides grounds for optimism that clinical tolerance will eventually become a reality.

Dendritic Cells↗