PubMed Health⌕ Search

Biomedical subjects

L Chan

Publications and source records attributed to L Chan.

At least 19 recordsLinked to original sources
PubMed2006

Sustained phenotypic correction in a mouse model of hypoalphalipoproteinemia with a helper-dependent adenovirus vector.

We examined the efficacy and host response to the adenovirus (Ad)-mediated delivery of human apolipoprotein A-I (APOA1) gene to the liver of APOA1(-/-) mice. Administration of a first-generation vector (FGAd-AI) resulted in a transient appearance of APOA1 in plasma and induced an anti-APOA1 antibody titer, whereas treatment with a helper-dependent vector (HDAd-AI) resulted in sustained APOA1 expression without inducing an antibody titer. With these results, we studied the effects of FGAd vectors on APOAI expression by HDAd-AI vector. Co-treatment with an FGAd vector inhibited HDAd-AI- mediated APOA1 expression independent of transgene cassettes, but only FGAd-AI induced a humoral response. Furthermore, APOA1 mRNA levels in mice co-treated with FGAd vectors were much lower than those expected from the vector copy number, suggesting that DNA of FGAd vectors interferes with the HDAd-AI vector's APOA1 promoter. A single treatment with an HDAd-AI vector produced a supraphysiological plasma APOA1 level that gradually declined to about half the normal human level over the course of 2 years, associated with a plasma cholesterol level that is persistently higher than that in controls. This investigation provides the proof of principle that liver-directed HDAd gene delivery is effective for the long-term phenotypic correction of monogenic hypoalphalipoproteinemia.

Adenoviridae↗
PubMed2006

Quality of life is predictive of survival in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Patients with unresectable hepatocellular carcinoma (HCC) have a dismal prognosis. The objective of this study was to evaluate whether patient-reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument is predictive of survival for these patients. MATERIALS AND METHODS: Two hundred and thirty-three patients with unresectable HCC (mainly hepatitis B-associated) who were recruited into two separate randomized phase III clinical studies, based on palliative chemotherapy and palliative hormonal therapy, respectively, gave consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and clinical variables at the time of study entry were analyzed to identify factors that influenced survival by applying multivariate analysis. Independent prognostic factors for survival were studied by Cox regression analysis. RESULTS: Median survival of the 233 patients was 5.5 months (95% CI 4.2-6.5 months). Significant independent predictors of shorter survival were advanced Okuda staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR = 1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10 point increase = 1.070). Patients who were entered into the chemotherapy trial (P = 0.0002; HR = 0.503), those who scored better in the physical functioning domain (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were associated with longer survival. CONCLUSIONS: In the studied HCC population, patient-reported baseline QoL provides additional prognostic information that supplements traditional clinical factors, and is a new prognostic marker for survival for patients with unresectable HCC.

Adolescent↗
PubMed2006

The significance of cutaneous spider naevi in children.

BACKGROUND: Cutaneous spider naevi are commonly considered to be a clinical sign of chronic liver disease. Little is known about their occurrence in children. AIM: To evaluate the occurrence of spider naevi in children with and without liver disease. METHODS: The presence of spider naevi was investigated in 460 children, 34 of whom had chronic liver disease. RESULTS: Of children without liver involvement, 38% had at least one spider naevus. The prevalence of spider naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more than five spiders present. Although eight of 10 children with cirrhosis had at least one spider naevus, only four of 34 children with chronic liver disease had five or more spiders present. Most spiders were on the hands and very few were >5 mm in size. CONCLUSIONS: Children with liver disease rarely have large numbers of spider naevi. Although the finding of five or more spider naevi is more common in liver disease, many normal children also have one or more of these lesions.

Adolescent↗
PubMed2006

Laparoscopic appendectomy significantly reduces length of stay for perforated appendicitis.

INTRODUCTION: Though ruptured appendicitis is not a contraindication to laparoscopic appendectomy (LA), most surgeons have not embraced LA as the first-line approach to ruptured appendicitis. In fact, in 2002, the Cochrane Database Review concluded: 1) the clinical effects of LA are "small and of limited clinical relevance," and 2) the effects of LA in perforated appendicitis require further study. OBJECTIVE: To study the effects of LA vs open appendectomy (OA) among adults with appendicitis. METHODS: In 2003, 272 adults underwent appendectomy at a large County hospital, and were enrolled in a prospective clinical pathway that detailed their hospital course from time of diagnosis to discharge. Data included patient demographics, time elapse from diagnosis to surgery, surgical technique (LA vs. OA), operative diagnosis (acute vs perforated appendicitis) and post-operative length of stay (LOS). RESULTS: Complete data was obtained for 264 (97%) patients. Patient demographics were similar in the LA and OA groups (p > 0.05). Patients with LA had a significantly shorter LOS than OA by 1.6 days (p < 0.05). This LOS was significantly shorter among those with ruptured appendicitis vs. non-ruptured appendicitis (2.0 days vs. 0.3 day reduction, p = 0.0357). Rank-order multiple regression analysis, controlling for all other factors, showed laparoscopy to have a significant effect on postoperative LOS in all appendicitis cases, especially ruptured appendicitis. CONCLUSIONS: The two-day reduction in LOS among those with ruptured appendicitis who underwent LA was significant enough to overcome the smaller benefit of LA in acute appendicitis. From a hospital utilization point of view, LA should be considered as the first-line approach for all patients with appendicitis.

Adult↗
PubMed2006

A randomised double-blinded controlled trial of the effect of diluent volume on the efficacy of a single dose of epidural ropivacaine for labour analgesia.

BACKGROUND: Few studies have systematically investigated the effect of diluent volume on the efficacy of epidural local anaesthetics for labour analgesia and no data are available for ropivacaine. Our aim was to compare epidural ropivacaine given in three different volumes for labour analgesia. METHODS: In a double-blinded study, we randomly assigned 60 labouring parturients with cervical dilatation <5 cm to receive epidural ropivacaine 30 mg diluted to 5 mL (group 5, n=20), 10 mL (group 10, n=20) or 20 mL (group 20, n=20) for analgesia. We measured visual analogue scale pain scores at the peak of contraction for 30 min plus onset and duration of analgesia. RESULTS: Pain scores at 30 min were similar among group 5 (median 22 [interquartile range 0-44] mm), group 10 (9 [0-21] mm) and group 20 (37 [0-51] mm), P=0.35. The number of patients who achieved a decrease in pain score to < or =30% of baseline was similar among group 5 (12/20 (60%)), group 10 (17/20 (85%)) and group 20 (11/19 (58%)), P=0.13. Onset and duration of analgesia, the incidence of motor block and patient satisfaction were similar among groups. CONCLUSIONS: Under the conditions of this study, within the range of 5-20 mL, the volume and concentration were not significant factors influencing the efficacy of a single 30-mg bolus of epidural ropivacaine given for labour analgesia. This suggests that the most important factor influencing analgesic efficacy was drug mass.

Adult↗
PubMed2006

Long-term safety and efficacy after conversion of maintenance renal transplant recipients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPA, myfortic).

AIM: A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium (EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population. METHODS: All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented. RESULTS: Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups. CONCLUSIONS: These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.

Adult↗
PubMed2005

Human health implications of environmental contaminants in Arctic Canada: A review.

The objectives of this paper are to: assess the impact of exposure to current levels of environmental contaminants in the Canadian Arctic on human health; identify the data and knowledge gaps that need to be filled by future human health research and monitoring; examine how these issues have changed since our first assessment [Van Oostdam, J., Gilman, A., Dewailly, E., Usher, P., Wheatley, B., Kuhnlein, H. et al., 1999. Human health implications of environmental contaminants in Arctic Canada: a review. Sci Total Environ 230, 1-82]. The primary exposure pathway for contaminants for various organochlorines (OCs) and toxic metals is through the traditional northern diet. Exposures tend to be higher in the eastern than the western Canadian Arctic. In recent dietary surveys among five Inuit regions, mean intakes by 20- to 40-year-old adults in Baffin, Kivalliq and Inuvialuit communities exceeded the provisional tolerable daily intakes (pTDIs) for the OCs, chlordane and toxaphene. The most recent findings in NWT and Nunavut indicate that almost half of the blood samples from Inuit mothers exceeded the level of concern value of 5 microg/L for PCBs, but none exceeded the action level of 100 microg/L. For Dene/Métis and Caucasians of the Northwest Territories exposure to OCs are mostly below this level of concern. Based on the exceedances of the pTDI and of various blood guidelines, mercury and to a lesser extent lead (from the use of lead shot in hunting game) are also concerns among Arctic peoples. The developing foetus is likely to be more sensitive to the effects of OCs and metals than adults, and is the age groups of greatest risk in the Arctic. Studies of infant development in Nunavik have linked deficits in immune function, an increase in childhood respiratory infections and birth weight to prenatal exposure to OCs. Balancing the risks and benefits of a diet of country foods is very difficult. The nutritional benefits of country food and its contribution to the total diet are substantial. Country food contributes significantly more protein, iron and zinc to the diets of consumers than southern/market foods. The increase in obesity, diabetes and cardiovascular disease has been linked to a shift away from a country food diet and a less active lifestyle. These foods are an integral component of good health among Aboriginal peoples. The social, cultural, spiritual, nutritional and economic benefits of these foods must be considered in concert with the risks of exposure to environmental contaminants through their exposure. Consequently, the contamination of country food raises problems which go far beyond the usual confines of public health and cannot be resolved simply by risk-based health advisories or food substitutions alone. All decisions should involve the community and consider many aspects of socio-cultural stability to arrive at a decision that will be the most protective and least detrimental to the communities.

American Indian or Alaska Native↗
PubMed2005

Gene therapy progress and prospects: gene therapy for diabetes mellitus.

Diabetes mellitus has long been targeted, as yet unsuccessfully, as being curable with gene therapy. The main hurdles have not only been vector-related toxicity but also the lack of physiological regulation of the expressed insulin. Recent advances in understanding the developmental biology of beta-cells and the transcriptional cascade that drives it have enabled both in vivo and ex vivo gene therapy combined with cell therapy to be used in animal models of diabetes with success. The associated developments in the stem cell biology and immunology have opened up further opportunities for gene therapy to be applied to target autoimmune diabetes.

Animals↗
PubMed2005

Broadband ultrasound attention reference database for southeast Asian males and females.

INTRODUCTION: The objective of this study was to establish the broadband ultrasound attenuation (BUA) measurements of the calcaneum for Southeast Asian males and females. A database was used to draw the reference curve for the Southeast Asian male and female population. MATERIALS AND METHODS: The database included 366 healthy females and 236 healthy males. We measured the BUA values of the left heel using the Contact Ultrasound Bone Analyser (CUBA) clinical system. RESULTS: The mean difference between Southeast Asian males and Caucasian males was 9.3 dB MHz-1 and that for females was 5.0 dB MHz-1. The standard deviations (SDs) for Southeast Asian female and male normative values were 17.43 and 20.10, respectively. This is comparable with the SD for the McCue Caucasian female and male normative data of 16.54 and 17.45 respectively. CONCLUSION: The study shows that the Southeast Asian population has a significantly lower normative value than the Caucasian population. This BUA reference database obtained will allow for more accurate determination of Southeast Asian patients at risk of osteoporosis.

Adult↗
PubMed2004

Sperm output of older men.

BACKGROUND: Declining fertility of couples from the fourth decade of life is largely attributable to the drop in female fertility. However, increasing numbers of men, whose fertility theoretically lasts until death, are seeking fertility treatment at older ages, yet there is little information on sperm production and function past the age of 50 years. The few studies of such older men have examined men attending fertility clinics, and therefore willing to provide semen samples, but the participation bias of such recruitment hinders extrapolation to the unselected general male population. METHODS: We have taken the opportunity to study a convenience sample of 55 healthy, non-infertile men ranging in age from 52 to 79 years old who provided semen samples as part of a prostate cancer screening project. They were compared with a control group (n = 409) of younger (< 52 years) men from among 567 volunteers screened as potential sperm donors for an artificial insemination program. RESULTS: Older men had lower semen volume (mean semen volume 1.8 versus 3.2 ml; P < 0.0001) and total sperm output (median 74 versus 206 million sperm per ejaculate; P < 0.0001), whereas sperm density (median 64 versus 73 million sperm/ml; P = 0.12) was non-significantly decreased. Older men had more abnormal sperm morphology with decreasing numbers of normal forms (mean 14% versus 25%; P < 0.0001) and reduced vitality (mean 51% versus 80%; P < 0.0001), as well as increased numbers of cytoplasmic droplets (median 1 versus 0; P < 0.0001) and sperm tail abnormalities (30% versus 17%; P < 0.0001). Sperm head or neck abnormalities were no different between the groups. CONCLUSIONS: While neither study group may be representative of the general male population, these findings suggest that sperm production, reflected in sperm output but not sperm density, as well as sperm morphology and viability are diminished in this population of healthy, non-infertile older men.

Aged↗
PubMed2004

Predictors of cardiovascular events and associated mortality within two years of kidney transplantation.

BACKGROUND: Cardiovascular disease is the most common cause of death after renal transplantation. Furthermore, acute coronary syndrome (ACS) attributable to coronary artery disease (CAD) accounts for the majority of deaths due to cardiovascular disease posttransplant. While renal transplantation is the treatment of choice for end-stage renal disease, understanding the causes of graft and patient loss is exceedingly important to improve outcomes. METHODS: This observational case-controlled study included 780 patients who underwent a kidney transplant between 1989 and 2001 who experienced early ACS (within 2 years). Patients were compared with controls matched for gender, year of transplant, and age. The primary outcome was the occurrence of an ACS event within 2 years after renal transplantation. RESULTS: Cardiovascular disease was the most common cause of death, with all 13 cardiovascular deaths due to CAD. An additional 15 episodes of nonfatal ACS episodes occurred. Thirty-seven percent of early ACS occurred perioperatively, the majority in the first 3 posttransplant months. On multivariate analysis, diabetes (OR [odds ratio] 5.56; P = .0007), smoking (OR 3.56; P = .034), and prior transplant (OR 2.81; P = .047) were associated with early ACS. CONCLUSIONS: Diabetes, smoking, and prior transplant were significantly associated with early ACS. The majority of events occurred perioperatively or within 3 months of transplant, highlighting the importance of improved screening and perioperative management.

Acute Disease↗
PubMed2004

Low-density lipoprotein receptor gene therapy using helper-dependent adenovirus produces long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia.

We tested the efficacy of low-density lipoprotein receptor (LDLR) therapy using helper-dependent adenovirus (HD-Ad), comparing it with that of very low-density lipoprotein receptor (VLDLR), an LDLR homolog. We treated high cholesterol diet fed LDLR-/- mice with a single intravenous injection of HD-Ad expressing monkey LDLR (1.5 x 10(13) or 5 x 10(12) VP/kg) or VLDLR. Throughout the 24-week experiment, plasma cholesterol of LDLR-treated mice was lower than that of VLDLR-treated mice, which was in turn lower than that of PBS-treated mice. Anti-LDLR antibodies developed in 2/10 mice treated with high-dose HD-Ad-LDLR but in none (0/14) of the other treatment groups. HD-Ad-treated mice displayed significant retardation of atherosclerotic lesion progression. We next tested the long-term efficacy of low-dose HD-Ad-LDLR injected into 12-week-old LDLR-/- mice. After 60 weeks, atherosclerosis lesions covered approximately 50% of the surface of aortas of control mice, whereas aortas of treated mice were essentially lesion-free. The lipid lowering effect of HD-Ad-LDLR lasted at least 108 weeks (>2 years) when all control mice had died. In addition to retarding lesion progression, treatment caused lesion remodeling from a vulnerable-looking to a more stable-appearing phenotype. In conclusion, HD-Ad-mediated LDLR gene therapy is effective in conferring long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia.

Adenoviridae↗
PubMed2004

The who, where, and what of rapid sequence intubation: prospective observational study of emergency RSI outside the operating theatre.

BACKGROUND: Emergency rapid sequence intubation (RSI) performed outside the operating room on emergency patients is the cornerstone of emergency airway management. Complication rates are unknown for this procedure in the United Kingdom and the factors contributing to immediate complications have not been identified. AIMS: To quantify the immediate complications of RSI and to assess the contribution made by environmental, patient, and physician factors to overall complication rates. METHODS: Prospective observational study of 208 consecutive adult and paediatric patients undergoing RSI over a six month period. RESULTS: Patients were successfully intubated by RSI in all cases. There were no deaths during the procedure and no patient required a surgical airway. Patient diagnostic groups requiring RSI are described. Immediate complications were hypoxaemia 19.2%, hypotension 17.8%, and arrhythmia 3.4%. Hypoxaemia was more common in patients with pre-existing respiratory or cardiovascular conditions than in patients with other diagnoses (p<0.01). Emergency department intubations were associated with a significantly lower complication rate than other locations (16.9%; p = 0.004). This can be explained by the difference in diagnostic case mix. Intubating teams comprised anaesthetists, non-anaesthetists, or both. There were no significant differences in complication rates between these groups. CONCLUSIONS: RSI has a significant immediate complication rate, although the clinical significance of transient events is unknown. The likelihood of immediate complications depends on the patient's underlying condition, and relevant diagnoses should be emphasised in airway management training. Complication rates are comparable between anaesthetists and non-anaesthetists. The significantly lower complication rates in emergency department RSI can be explained by a larger proportion of patients with comparatively stable cardiorespiratory function.

Adolescent↗
PubMed2004

Bispectral index during modified rapid sequence induction using thiopentone or propofol and rocuronium.

This randomized controlled trial compared Bispectral Index (BIS) values in 40 patients after a modified rapid sequence induction using thiopentone 4 mg/kg or propofol 2 mg/kg with rocuronium 0.6 mg/kg as muscle relaxant. Endotracheal intubation was performed at 60 seconds from induction of anaesthesia and BIS values were recorded for three minutes after induction. At the 120, 150 and 180 second measurements there was a significantly greater proportion of subjects with BIS values < or = 60 ("anaesthetized") in the propofol group compared with the thiopentone group (P values < 0.02, < 0.01 and < 0.01 respectively). All intubations were completed within two minutes. No explicit recall of intubation was detected clinically with either induction agent. The BIS scores we have measured suggest that thiopentone 4 mg/kg is more likely to be associated with lighter planes of anaesthesia and consequent risk of awareness than propofol 2 mg/kg, if intubation is delayed or prolonged.

Adult↗
PubMed2003

Obesity as an independent predictor of posttransplant diabetes mellitus.

BACKGROUND: In the general population, there is a clear association between obesity and type 2 diabetes mellitus. However, the evidence of relationship between body mass index (BMI: weight/height(2)) and the risk of posttransplant diabetes mellitus (PTDM) is inconsistent when studied at a level of single center. The aim of our study was to determine if pretransplant BMI is an independent risk factor for PTDM at our center and to demonstrate the pattern of weight gain in patients who develop PTDM. METHODS: This is a retrospective analysis of renal allograft recipients at University of Colorado Hospital. The medical records of patients who received a kidney transplant from January 1998 to March 2001 were screened to identify the cases of PTDM. Controls were matched for immunosuppressive regimen, gender, and type of donor. A total of 18 cases and 36 controls were identified. RESULTS: The incidence of PTDM in our transplant population was 10%. Of these cases, 72% developed PTDM in the first 2 months after transplant, and 38% of them required insulin. On multivariate analysis, BMI was significantly associated with PTDM (adjusted odds ratio 1.22, 95% confidence interval 1.04-1.42) while controlling for number of rejections, age, and other factors. We also noticed that weight gain was significantly lower in patients who developed PTDM after transplantation. CONCLUSIONS: We conclude that obesity is an independent predictor of PTDM. The weight gain was significantly poor among patients who developed PTDM. Among all the risk factors for PTDM, obesity is the only modifiable risk factor before transplantation. Obese patients should be treated with a less diabetogenic immunosuppressive regimen and be counseled to lose weight before transplant.

Adult↗
PubMed2003

Upregulation of IL-2 but not IL-15 by allorecognition in human mixed lymphocyte culture.

The redundant and pleiotropic effects of cytokines in transplant models have been shown both in vitro and in vivo. IL-2 is clearly not necessary for allograft rejection, possibly due to upregulated IL-15. We examined IL-15 expression using mixed lymphocyte culture (MLC) as an allorecognition model. IL-2 and IL-15 levels were measured by enzyme-linked immunoassay after 120 hours of culture. Cell proliferation in MLC was examined using [(3)H]thymidine uptake in the presence of either anti-IL-2Ralpha chain antibody or anti-IL-2Rgamma chain antibody. While IL-2 was detectable in cell supernates of MLC, IL-15 was not. Stimulation with an Anti-IL-2 gamma chain antibody which blocks the IL-2 gamma chain, a common unit in IL-2/IL-15 receptors, failed to produce additive antiproliferative effects after maximum inhibition by anti-IL-2alpha chain antibody, which is specific for IL-2. In conclusion, experiments in the MLC model suggest that allorecognition upregulates IL-2 but not IL-15 expression.

Cell Division↗