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F Chan

Publications and source records attributed to F Chan.

At least 19 recordsLinked to original sources
PubMed2000

Substituted benzamide inhibitors of human rhinovirus 3C protease: structure-based design, synthesis, and biological evaluation.

A series of nonpeptide benzamide-containing inhibitors of human rhinovirus (HRV) 3C protease was identified using structure-based design. The design, synthesis, and biological evaluation of these inhibitors are reported. A Michael acceptor was combined with a benzamide core mimicking the P1 recognition element of the natural 3CP substrate. alpha,beta-Unsaturated cinnamate esters irreversibly inhibited the 3CP and displayed antiviral activity (EC(50) 0.60 microM, HRV-16 infected H1-HeLa cells). On the basis of cocrystal structure information, a library of substituted benzamide derivatives was prepared using parallel synthesis on solid support. A 1.9 A cocrystal structure of a benzamide inhibitor in complex with the 3CP revealed a binding mode similar to that initially modeled wherein covalent attachment of the nucleophilic cysteine residue is observed. Unsaturated ketones displayed potent reversible inhibition but were inactive in the cellular antiviral assay and were found to react with nucleophilic thiols such as DTT.

3C Viral Proteases↗
PubMed2000

Current epidemiology of human plague in Madagascar.

From 1996 to 1998, 5,965 patients with suspected plague were identified in 38 districts of Madagascar (40% of the total population are exposed). Using standard bacteriology, 917 of them were confirmed or presumptive (C + P) cases. However, more than 2,000 plague cases could be estimated using F1 antigen assay. Two out of the 711 Yersinia pestis isolates tested were resistant to chloramphenicol and to ampicillin (both isolates found in the harbour of Mahajanga). Urban plague (Mahajanga harbour and Antananarivo city) accounted for 37.4% of the C + P cases. Bubonic plague represented 97.2% of the cases, and the lethality rate was still high (20%). In comparing the exposed population, plague was more prevalent in males (M:F sex ratio 1.3:1) and patients under 20 years (2.7% babies under two years). Buboes were mainly localised in the inguinal/femoral regions (55.8%). The epidemiological risk factors are discussed.

Adolescent↗
PubMed2000

Performance of the ImmunoCard STAT! E. coli O157:H7 test for detection of Escherichia coli O157:H7 in stools.

ImmunoCard STAT! E. coli O157:H7 (Meridian Diagnostics, Inc., Cincinnati, Ohio) is a novel rapid (10-min) test for the presence of Escherichia coli O157:H7 in stools. The test may be performed either directly on stool specimens or on an overnight broth culture of stool. In a multicenter prospective study, 14 of 14 specimens positive by culture for E. coli O157:H7 were positive by the ImmunoCard STAT! O157:H7 test, and there were no false positives from 263 culture-negative specimens. In a retrospective study, the test was positive in 339 (81%) of 417 stored culture-positive specimens and the specificity was 95% (98 of 103 specimens). No false positives were associated with alternate stool pathogens. The ImmunoCard STAT! O157:H7 test has high sensitivity and specificity.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Risk factors for resistance to "first-line" antimicrobials among urinary tract isolates of Escherichia coli in children.

BACKGROUND: There are increasing concerns regarding antimicrobial resistance in Canada. Data are limited on the prevalence, patterns of resistance and risk factors associated with resistant organisms, including coliforms, in children. This study was done to address these issues as they relate to urinary tract isolates of Escherichia coli in a tertiary care pediatric centre in Ottawa. METHODS: A surveillance study was conducted from December 1992 to December 1994. Susceptibility testing of urinary tract isolates of E. coli was performed using a panel of antimicrobial agents. A case-control study was also conducted for subjects with isolates resistant to trimethoprim-sulfamethoxazole (T-S), this drug being used a representative "first-line" agent. RESULTS: A total of 1636 consecutive isolates were obtained from 967 subjects. Of the 1636 isolates, 736 (45.0%) were resistant to ampicillin, 514 (31.4%) were resistant to T-S, 363 (22.2%) were resistant to both ampicillin and T-S, and 27 (1.7%) were resistant to both ampicillin and gentamicin. In the case-control study 274 children with isolates resistant to T-S were matched with 274 children who had T-S-sensitive isolates obtained during the study period or the preceding or subsequent 6 months. Multivariate analyses indicated that subjects who had received antimicrobials for more than 4 weeks in the previous 6 months were about 23 times more likely to have isolates resistant to T-S than were subjects without this risk factor (odds ratio [OR] 23.4, 95% confidence interval [CI] 12.0-47.6). Children with genitourinary tract abnormalities were 2.4 times more likely to have resistant isolates than those without such abnormalities (95% CI 1.2-4.5). Compared with children who had no hospital admissions in the previous year, those with 1 admission in that period were more likely to have resistant isolates (OR 2.3, 95% CI 1.4-7.5), as were those with 2 or more admissions in that period (OR 3.2, 95% CI 1.1-4.8). Compared with children aged 2-6 years, children under 2 years of age were less likely to have resistant isolates (OR 0.3, 95% CI 0.2-0.8). INTERPRETATION: Selective antimicrobial pressure and multiple admissions to hospital were among the risk factors associated with antimicrobial resistance. The finding of a low but definite level of resistance to both ampicillin and gentamicin is important for the selection of empiric therapy for sepsis in neonates. The role of inexpensive first-line agents in the outpatient treatment and prevention of urinary tract infections requires re-examination, particularly in children who have recently received antimicrobial therapy.

Anti-Bacterial Agents↗
PubMed1999

Idiopathic dilated cardiomyopathy presenting in pregnancy.

PURPOSE: To describe the clinical course and management of a patient who presented with idiopathic dilated cardiomyopathy in early pregnancy. CLINICAL FEATURES: A 27 yr old, previously well, Chinese primigravida presented at 18 wk gestation with a history of irregular heart beat and decreased exercise tolerance. Echocardiography showed moderate left ventricular dysfunction with left ventricular ejection fraction of 35-40%. Idiopathic dilated cardiomyopathy was diagnosed. She declined termination of pregnancy and was managed medically with furosemide, digoxin and potassium supplements. Low molecular weight heparin was prescribed. Emergency Cesarean delivery was performed at 31 wk gestation because of deteriorating liver function and a non-reassuring fetal heart rate pattern. General anesthesia was given because of relative urgency, the patient's wish, and concerns about potential risk of spinal hematoma. Invasive monitoring with pulmonary and radial artery catheters was used and low dose inotropic support was given. Postoperatively, she was managed in the intensive care and coronary care units where she was treated with dobutamine, furosemide, digoxin, potassium, captopril, losartin and warfarin. Her postoperative course was complicated by a severe embolic stroke five weeks after delivery and she died five months later. CONCLUSION: Idiopathic dilated cardiomyopathy may rarely present in pregnancy. A multidisciplinary approach and close peripartum monitoring are important in management and termination of pregnancy should be considered. Thromboembolic complications are a major risk.

Adult↗
PubMed1999

Patency and limb salvage for polytetrafluoroethylene bypasses with vein interposition cuffs.

Polytetrafluoroethelene (PTFE) is often utilized in patients with limb-threatening ischemia requiring infrainguinal revascularization in the absence of autologous saphenous vein. To increase long-term patency of PTFE grafts, vein interposition cuffs have been recommended as adjunctive procedures. The purpose of this study was to assess the efficacy of vein interposition cuffs on the long-term patency and limb salvage of patients requiring prosthetic bypass grafts for limb-threatening ischemia. Prosthetic bypass grafts with vein interposition cuffs (PTFE/VC) were performed on 56 limbs in 55 patients (32 men, 23 women; mean age of 67 years) from October 1993 to January 1998. Grafts were prospectively evaluated every 3 months for the first 12 months and biannually thereafter with duplex ultrasonography. PTFE/VC and PTFE bypasses at the popliteal level appear to have comparable patencies. However, PTFE/VC appear to offer an improved patency and limb salvage for infrapopliteal bypasses in patients with critical limb ischemia. When infrapopliteal revascularization is required in the absence of autologous saphenous vein, we recommend the use of PTFE with vein interposition cuffs.

Aged↗
PubMed1999

Advances in imaging techniques for the diagnosis of focal hepatic lesions.

In the past few years, tremendous advances have been made in the fields of ultrasound, computed tomography, magnetic resonance imaging and contrast agent development. The purpose of this article is to highlight the important developments in imaging techniques that can be used for detection and characterization of focal hepatic lesions.

Aged↗
PubMed1999

New approaches to the investigation of focal hepatic lesions.

In the past few years, tremendous advances have been made in the fields of magnetic resonance imaging, computed tomography and ultrasonography. These include the development of novel contrast agents and new approaches to image acquisition and processing. This review provides an overview of the state-of-the-art of imaging investigation of focal hepatic lesions and highlights some of the most exciting emerging technologies.

Diagnosis, Differential↗
PubMed1999

Gastrostomy tubes in patients with recurrent gynaecological cancer and intestinal obstruction.

OBJECTIVE: Women with recurrent gynaecological cancers who are not suitable for exenterative surgery commonly present with gastrointestinal dysfunction. This paper is a retrospective review of the use of gastrostomy tubes in such women. METHODS: We performed a chart review of women with recurrent gynaecological cancer who had a gastrostomy tube placed between January 1991 and April 1998. RESULTS: Thirty-nine women (mean age 53.2 years, range 17-82) had a gastrostomy tube placed. Twenty-eight (72%) had ovarian cancer, eight (21%) had cervical cancer, two had endometrial cancer and one had vaginal cancer. In 14 women a gastrostomy tube was placed as the sole procedure for palliation (11 elective, 3 emergency). In the remaining 25 women, who underwent major surgery, a gastrostomy tube was placed in anticipation of, or in the presence of, significant intestinal distension and expected prolonged post-operative ileus. Eleven women (28%) died without leaving hospital after their operation (median 11 days, range 2-36). All but one of the 28 women who left hospital had satisfactory oral intake. Twenty-one women (54%) died with the gastrostomy tube in place (median 28 days, range 2-157) and 18 (46%) had the gastrostomy tube removed (median 14.5 days, range 9-180), 13 of whom (33%) have since died (median 167 days, range 77 days-7 years). Five women (13%) are alive (median 2.2 years, range 10 months-4.5 years). There were no problems which required the gastrostomy tube to be removed. CONCLUSION: Gastrostomy tubes have an important role in the treatment of women with recurrent gynaecological cancer, allowing gastric drainage and decompression without the disadvantages of nasogastric tubes.

Acute Disease↗
PubMed1999

Argument for the surgical staging of apparent early endometrial cancer.

Cancer of the uterine corpus, commonly referred to as cancer of the endometrium or cancer of the uterus, continues to be the most common pelvic genital malignancy affecting western women (1). In 1998 in the United States 36,100 women were diagnosed with this cancer, and there were 6,300 deaths from this condition in that year. Of concern is that despite a relatively stable incidence over the last decade, the annual number of deaths since 1987 from endometrial cancer has more than doubled (2). Many controversies exist in the management of apparent early endometrial cancer. These include: 1. The role of surgical staging which includes pelvic lymphadenectomy. 2. The role of the subspecialist gynaecological oncologist in primary surgical treatment. 3. Indications for vaginal and external beam radiotherapy. 4. Who is at risk for recurrence? 5. The role of laparoscopic approach to the management of this disease. Despite their importance, these and other issues have not been appropriately addressed by prospective randomized studies. Treatment strategies and algorithms have thus been based upon a combination of clinicopathological studies and uncontrolled reviews. The views expressed in this clinical opinion are those of the Sydney Gynaecologic Oncology Group and reflect our philosophy on the current management of this tumour, supported by recent and appropriate peer reviewed scientific literature.

Brachytherapy↗
PubMed1998

Epidemiology of methicillin-resistant Staphylococcus aureus in three Canadian tertiary-care centers.

OBJECTIVE: To describe the epidemiology and spread of methicillin-resistant Staphylococcus aureus (MRSA) in three tertiary-care centers in Ottawa, Ontario, Canada, where MRSA is encountered infrequently. DESIGN: Retrospective review over a 6-year period, from January 1, 1990, through December 31, 1995. SETTING: Three tertiary-care teaching hospitals in Ottawa. PARTICIPANTS: Patients and healthcare workers (HCWs) with MRSA isolated from any body site. METHODS: Patients and HCWs were identified retrospectively through hospital microbiology and infection control records. Patient charts were reviewed for clinical and epidemiological data, including age, gender, previous hospital admissions (where noted), and current and recent antibiotic use. MRSA isolates that were available were typed using pulsed-field gel electrophoresis (PFGE). Methicillin resistance was confirmed by standard methods and by polymerase chain reaction using mecA-specific primers. RESULTS: MRSA was identified in 53 patients and 2 HCWs. Three patients were excluded from further analysis because medical records were incomplete. Epidemiological data were collected on the remaining 52 individuals. Thirty-nine isolates from 31 patients and 2 HCWs were available for PFGE typing. Five epidemiologically linked nosocomial clusters involving 10 patients and 2 HCWs were identified and were confirmed by PFGE. MRSA isolates from a sixth cluster were not available for PFGE. In each cluster, nosocomial spread was minimized by standard infection control practices, including strict isolation of patients and screening of contacts. There was no evidence of secondary spread of MRSA involving the remaining 36 patients. Recent antibiotic use, surgery, admission to an intensive-care unit, and previous hospitalization were common among patients. There was no evidence of spread of MRSA among the three hospitals, and no endemic strains were apparent in any of these centers. CONCLUSIONS: MRSA remains an infrequent isolate in our centers, with no apparent interhospital spread. In institutions with little or no endemic MRSA, rigorous application of standard infection control practices is effective in limiting nosocomial transmission of this organism.

Hospitals, Teaching↗
PubMed1998

Sensitivities and specificities of premier E. coli O157 and premier EHEC enzyme immunoassays for diagnosis of infection with verotxin (Shiga-like toxin)-producing Escherichia coli. The SYNSORB Pk Study investigators.

This study describes the performance of two rapid enzyme immunoassays, Premier E. coli O157 and Premier EHEC (Meridian Diagnostics Inc., Cincinnati, Ohio) for the detection in stools of Escherichia coli O157 and verotoxins (Shiga-like toxins), respectively. Both tests were performed on stools from 876 children presenting to eight emergency departments with diarrhea. Standard culture, including E. coli O157:H7 isolation, was performed, and paired sera were taken for anti-O157-lipopolysaccharide antibody determination. Stools from patients enrolled in the study, and those yielding discordant results, were sent to a reference laboratory for repeat testing and further investigation, including cytotoxicity and non-O157 verotoxin-producing E. coli culture. Results were classified as field results (obtained in the eight site laboratories) and resolved results (obtained after repeat testing in the central laboratory). The "gold standard" for sensitivity of both tests and for specificity of Premier E. coli O157 was isolation of E. coli O157:H7 or a fourfold anti-O157 antibody rise. Specimens positive by the Premier EHEC test and negative for E. coli O157 culture were examined for non-O157 verotoxin-producing E. coli. The field sensitivity of Premier E. coli O157 was 86%, that of Premier EHEC was 89%, and the specificity of Premier E. coli O157 was 98%. Ten of 13 discordant Premier E. coli O157 results were reassigned as true results after repeat testing. Ten non-O157 verotoxin-producing E. coli isolates were recovered from Premier EHEC-positive, E. coli O157 culture-negative stools. Only one specimen gave an unequivocally false-positive Premier EHEC result. Both tests are highly sensitive and are specific if correctly performed. The Premier EHEC test will be particularly valuable as a practical routine test for the detection of non-O157 verotoxin-producing E. coli.

Antibodies, Bacterial↗
PubMed1997

Development and application of the Family Involvement Questionnaire in brain injury rehabilitation.

This article reports the development and implementation of a new instrument, the Family Involvement Questionnaire (FIQ), for determining perceptions about family involvement needs in the rehabilitation process of traumatically brain-injured (TBI) clients. Factor analysis results indicate a four-factor solution to be optimal both in terms of parsimony and psychological meaningfulness, providing empirical evidence for the factorial structure of the FIQ. Additional statistical analyses using the factor-based scores of the four FIQ subscales revealed that professionals and family members differ significantly in their perceptions regarding family involvement in TBI rehabilitation in three of the four subscales. Specific activities where family members and professionals differed significantly are explored and implications of the study are discussed.

Analysis of Variance↗
PubMed1997

Insulin-like growth factor-I in men with idiopathic osteoporosis.

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bone formation in men with idiopathic osteoporosis may be related to deficiencies in skeletal mechanisms that are mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men (50.5 +/- 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score -3.5 +/- 0.16) were studied. The following biochemical indices were all normal: serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid hormone level was in the lower range of normal, 25 +/- 2 pg/mL (nl: 10-65). Mean serum IGF-I level was also in the lower range of normal, 157.9 +/- 7.6 ng/mL (normal age-matched range, 140-260 ng/mL). Eight men had IGF-I levels that were below 140 ng/mL. The mean IGF-IZ score was -0.75, significantly different from the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin concentration correlated well with bone density at the distal 1/3 radius (r = +0.44; P < 0.002). Histomorphometric analysis of bone biopsy specimens showed significant reductions in cancellous bone volume (31%; P < 0.001), cortical width (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when results were compared with age-matched control subjects. Percent eroded surface was normal and was correlated inversely with serum IGF-I levels (r = -0.5; P < 0.04). These results suggest that serum IGF-I levels are reduced in men with idiopathic osteoporosis and that IGF-I correlates with and may contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF-I levels may reflect the reduction in bone formation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies of the IGF-I axis.

Adult↗
PubMed1996

Prevalence of Dientamoeba fragilis antibodies in children and recognition of a 39 kDa immunodominant protein antigen of the organism.

Dientamoeba fragilis, a common intestinal protozoan parasite in Canada, has been associated with diarrhoea and abdominal pain in some patients. Seroprevalence of this organism has not been reported previously. In the present study sera from three symptomatic patients, 12 age- and sex-matched controls, and 189 randomly selected healthy individuals (age 6 months to 19 years) were tested for antibodies against Dientamoeba fragilis by an indirect immunofluorescence (IIF) assay. All three symptomatic patients infected with Dientamoeba fragilis had positive IIF titres of 80, and all 12 matched controls had positive titres ranging 20 to 160 (geometric mean titre 48). Of the 189 healthy children, 172 (91%) were positive at a serum dilution of 1:10 or higher. The specificity of the IIF assay was reinforced by immunoblotting 20 representative serum samples against Dientamoeba fragilis. In all 17 IIF-positive serum samples, a 39 kDa protein band of Dientamoeba fragilis was identified, the same band recognized by a mouse monoclonal antibody raised in our laboratory. Findings over a five-year period indicate that Dientamoeba fra-gilis was the most common protozoan, followed closely by Giardia lamblia and more distantly by Cryptosporidium parvum. The high seropositivity of 91% for Dientamoeba fragilis compares reasonably well with serologic data obtained by IIF and reported previously for Giardia lamblia (85.6%) and Cryptosporidium parvum (86%).

Adolescent↗
PubMed1996

Total and functional antibody response to a quadrivalent meningococcal polysaccharide vaccine among children.

OBJECTIVE: To determine total and functional serogroup C antibody response after vaccination with a quadrivalent meningococcal polysaccharide vaccine. DESIGN: Prospective, before and after intervention study. SUBJECTS: Study subjects were between the ages of 0.5 and 19.9 years, and were eligible for a community-wide public health immunization campaign against Neisseria meningitidis serogroup C. METHODS: Total and functional antibody response was measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: One month after vaccination, total capsular polysaccharide antibody significantly increased in all age groups; a significant rise in bactericidal antibody, that correlated with total capsular polysaccharide antibody, was seen in children 18 months of age and older. At 1 year bactericidal antibody titers were maintained but capsular polysaccharide antibody declined substantially in children younger than 5 years. CONCLUSION: Total capsular polysaccharide antibody concentration appears to be a useful surrogate measure of bactericidal antibody in children 18 months and older. Children who originally received the vaccine at less than 18 months of age should be considered for revaccination if there is a new or continuing risk of disease. Because of the differences in the total and bactericidal antibodies formed, vaccine efficacy trials are required to define which serologic measures are associated with protection.

Adolescent↗
PubMed1996

An assessment of the validity of ICD Code 410 to identify hospital admissions for myocardial infarction: The Corpus Christi Heart Project.

BACKGROUND: The identification of myocardial infarction (MI) is typically based on finding events designated by a nosologist with the appropriate International Classification of Diseases (ICD) code, currently code 410. These codes are applied based on review of medical records or death certificates. However, other factors, including reimbursement considerations, may influence the coding process, especially for hospitalizations. Thus, the validity of using ICD code 410 to identify MI must be assessed. METHODS: The Corpus Christi Heart Project (CCHP) is a population-based surveillance programme for hospitalized MI. Patients were identified using concurrent ascertainment in coronary care units and retrospective review of medical records. Events were validated as definite or possible MI using data regarding chest pain, electrocardiographic changes and cardiac enzymes. The validity of using ICD code 410 to identify cases of MI was assessed by calculating the sensitivity, specificity, predictive values and efficiency of ICD code 410 versus the CCHP 'gold standard'. RESULTS: Use of ICD code 410 identified 80.9% (401/496) of definite MI, but only 19.0% (243/1280) of possible MI. Only 12.3% (90/734) of discharges with an ICD 410 code received a 'no MI' designation based on the 'gold standard'. The efficiency of ICD code 410 for identifying MI was 92.0% for definite MI and 77.1% for definite and possible MI. CONCLUSIONS: The use of ICD code 410 to identify hospitalized cases of MI results in a modestly biased overestimate of the number of definite MI hospitalizations; however, this approach warrants consideration due to the expense of validation procedures.

Adult↗