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Biomedical subjects

E Chan

Publications and source records attributed to E Chan.

At least 55 records · Page 3Linked to original sources
PubMed2000

A randomized controlled trial of azithromycin and amoxycillin/clavulanate in the management of subacute childhood rhinosinusitis.

OBJECTIVE: Subacute childhood rhinosinusitis is a disorder commonly seen in children with allergic rhinitis. Antibiotics have been recommended as a major component of the treatment regime. The objective of the present study was to compare the effectiveness of a 3-day course of azithromycin and a 2-week course of amoxycillin/clavulanate in the treatment of subacute childhood rhinosinusitis. METHODOLOGY: A randomized single-blinded control study of subacute rhinosinusitis was conducted, comparing a 3-day course of azithromycin and a 2-week course of amoxycillin/clavulanate. Inclusion criteria were children aged between 5 and 16 years, duration of nasal blockage or discharge between 30 and 120 days, and abnormal sinus radiographs. All enrolled children were prescribed budesonide nasal spray (Rhinocort Aqua Nasal Spray, Astra Pharmaceuticals, Sodertalje, Sweden) as adjuvant treatment. RESULTS: Forty-two children were recruited into the study and one defaulted on follow-up. Failure occurred in 6 of 20 for the azithromycin group and 5 of 21 for the amoxycillin/clavulanate group. The odds ratio was 1.46 (95%CI 0.37-5. 80, P = 0.73). No relapse occurred in azithromycin group and 5 of 21 in amoxycillin/clavulanate group. The odds ratio was 0.16 (95%CI 0. 017-1.51, P = 0.18). Both antibiotics were well tolerated, however, two children, one from each group, complained of mild transient epigastric discomfort. CONCLUSIONS: This small study did not provide evidence of a difference between 14 days of amoxycillin/clavulanate and 3 days of azithromycin. Larger studies will be needed to determine which, if any, antibiotic regimen should be used in treating subacute childhood rhinosinusitis.

Adolescent↗
PubMed2000

The use of variable pulse width frequency doubled Nd:YAG 532 nm laser in the treatment of port-wine stain in Chinese patients.

BACKGROUND: Variable pulse width frequency doubled Nd:YAG 532 nm laser has previously been shown to be effective in the treatment of vascular lesions in Caucasians. For dark-skinned patients, such as Asians, its role has not been determined. OBJECTIVE: To assess the clinical efficacy and complication rate of the 532 nm Nd:YAG laser in the treatment of port-wine stain in Chinese patients. METHODS: Chinese patients with port-wine stain who had undergone Nd:YAG laser treatment were called for questionnaire assessment of their degree of clearing and clinical examination for complications by two independent observers. For 22 patients with pre- and posttreatment photographs, the two independent observers further assessed the degree of clearing. RESULTS: Assessment of the questionnaire indicated that 62.9% of the patients subjectively considered that they had more than 25% clearing, with 33.3% having more than 50% clearing. For those with pre- and posttreatment photographs, the objective degree of improvement was less impressive with 18.1% of patients having at least 25% improvement and only 13.6% having more than 50% improvement. Pigmentary and texture changes were seen in both groups (33% in group I and 11% in group II). The number of treatment sessions rather than previous use of pulsed dye laser therapy was an important risk factor for complications. CONCLUSION: Nd:YAG laser is only partially effective for the treatment of port-wine stain in Chinese patients. Although most patients recorded some degree of subjective improvement, many did not improve by objective assessment. High fluence is necessary to achieve the desirable clinical response, and while contact cooling reduces the risk of epidermal damage, texture changes can still occur. Further study is necessary to compare its use with other similar devices, such as a pulsed dye laser with cryogen spray cooling.

Adult↗
PubMed2000

Enhancement by ampicillin of antibody responses induced by a protein antigen and a DNA vaccine carried by live-attenuated Salmonella enterica serovar Typhi.

Live-attenuated Salmonella species are effective carriers of microbial antigens and DNA vaccines. In a mouse model, the immunoglobulin M (IgM) and total antibody levels directed toward the lipopolysaccharide of Salmonella enterica serovar Typhi were significantly enhanced at day 21 after oral immunization with live-attenuated serovar Typhi (strain Ty21a) when ampicillin was concomitantly administered (P < 0.05 and P < 0.005, respectively). The heat-killed Ty21a-stimulated lymphocyte proliferation indices for the ampicillin group at day 21 were significantly higher than those for the normal saline (NS) group (P < 0.005, P < 0.001, and P < 0.01) for all three doses of antigen (10(4), 10(5), and 10(6) heat-killed Ty21a per well, respectively). The 50% lethal doses for mice from the ampicillin and NS groups immunized with Ty21a with pBR322 after wild-type serovar Typhi challenge on day 24 were 3.4 x 10(7) and 5.0 x 10(6) CFU, respectively. The fecal bacterial counts for the ampicillin group at days 1, 3, and 5 were significantly lower than those for the NS group (P < 0.01, P < 0.01, and P < 0.05, respectively), and there was a trend toward recovery of Ty21a in a larger number of mice from the ampicillin group than from the NS group. Furthermore, the IgG2a levels directed toward tetanus toxoid were significantly enhanced at days 7 and 21 after oral immunization with Ty21a that carried the fragment c of tetanus toxoid when ampicillin was concomitantly administered (P < 0.05 and P < 0.005, respectively), and the IgM and total hepatitis B surface antibody levels were significantly enhanced at days 7 (P < 0.005 and P < 0.05, respectively) and 21 (P < 0.01 and P < 0.05, respectively) after oral immunization with Ty21a that carried the DNA vaccine that encodes hepatitis B surface antigen when ampicillin was concomitantly administered. The present observation may improve the efficacy of the protein antigens and DNA vaccines carried in live-attenuated bacteria, and further experiments should be carried out to determine the best antibiotics and dosage regimen to be used, as well as the best carrier system for individual protein antigens and DNA vaccines.

Ampicillin↗
PubMed2000

Cost analysis of an adult outpatient parenteral antibiotic therapy (OPAT) programme. A Canadian teaching hospital and Ministry of Health perspective.

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) programmes have become prevalent over the past 2 decades. From the US perspective, these programmes have been shown to reduce healthcare costs. No comprehensive analysis has been published from the Canadian perspective. OBJECTIVE: To describe a Canadian OPAT programme for the 3-year period since its inception and to conduct a treatment cost analysis. DESIGN AND METHODS: Demographics and resource utilisation data (health professional labour, laboratory and diagnostic tests, antimicrobials, delivery, home nursing care, catheters and catheter placement) were prospectively collected for enrollees in the OPAT programme over the evaluation period. Avoided hospital resource utilisation was estimated via retrospective chart review by the investigators. Costs were retrospectively assigned to each resource and total cost avoidance by the OPAT programme was determined from each perspective. PERSPECTIVE: A teaching hospital and a provincial Ministry of Health (MOH). MAIN OUTCOME MEASURES AND RESULTS: 140 treatment courses were initiated for 117 adult patients (mean age 54 years) who were enrolled into the programme. Mean pre-OPAT length of hospital stay was 12 days, and mean OPAT duration was 22.5 days. Bone/joint (39%), skin and soft tissue (16%), cardiac (13%) and respiratory tract (12%) infections were the most common infections managed. The most commonly used antimicrobials were vancomycin (29%), cloxacillin +/- gentamicin (22%) and ceftriaxone +/- gentamicin (11%) 85% of enrollees successfully completed their planned antimicrobial treatment regimens. Premature discontinuation of antimicrobial therapy for various reasons occurred in the remaining 15% of courses. The mean cost per treatment course of OPAT was 1910 Canadian dollars ($Can) from the hospital perspective and $Can6326 from the MOH perspective. Assuming that patients would have otherwise completed their antimicrobial therapy in hospital, the mean cost per treatment course was estimated to be $Can14,271. The overall cost avoidance of the OPAT programme was $Can1,730,520 (hospital perspective) and $Can1,009,450 (MOH perspective) over the 3-year assessment period. Sensitivity analyses revealed the results to be robust to plausible changes. CONCLUSIONS: This analysis supports the premise that an adult OPAT programme can substantially reduce healthcare costs in the Canadian healthcare setting.

Adolescent↗
PubMed2000

Treatment of in-stent coronary restenosis with excimer laser angioplasty.

OBJECTIVE: To evaluate the efficacy and safety of excimer laser coronary angioplasty (ELCA) with adjunctive balloon angioplasty in patient with in-stent restenosis. METHODS: ELCA was performed in 20 patients of instent restenosis. All patients were symptomatic and had class III-IV angina. ELCA was performed with the Spectranetics CVX-300 System. The laser catheter of Vittesse C (concentric) and E (eccentric) with diameter of 1.4-2.0 mm was used. RESULTS: Laser catheter crossed all stenotic stents without difficulty. The lesion length was 4.6-51.2 mm, mean 20.7 +/- 13.7 mm, including 14 lesions > 10 mm. Laser treatment alone increased minimal lumen diameter (MLD) from 0.3 +/- 0.3 mm to 1.4 +/- 0.3 mm (P < 0.0001) and improved the diameter stenosis from 88.8% +/- 10.0% to 46.0% +/- 8.0% (P < 0.0001). Adjunctive balloon angioplasty further increased minimal lumen diameter to 2.3 +/- 0.7 mm and reduced diameter stenosis to 14.2% +/- 8.2% (P < 0.0001). At follow-up (1-17 months, mean 8.9 +/- 5.7 months), 17 (85%) patients had remained asymptomatic, 3 (15%) patients had mild to moderate exertional angina, 1 (5%) patient received CABG. CONCLUSION: ELCA with adjunctive percutaneous transluminal coronary angioplasty (PTCA) is an efficient and safe technique to debulk tissue in the patient with in-stent restenosis. The incidence of procedural related complication was low and ELCA may be used as a good method for in-stent restenosis treatment.

Aged↗
PubMed1999

Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects.

The average daily consumption of seal oil by the Inuit people is approximately 8-9 g, yet there is very little information on the effect of seal oil consumption on cardiovascular disease risk factors. In this study, 19 healthy, normocholesterolemic subjects consumed 20 g of encapsulated seal oil containing eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and docosapentaenoic acid (DPA; 22:5n-3) or 20 g of vegetable oil (control) per day for 42 days. Levels of selected cardiovascular and thrombotic risk factors as well as fatty acid profiles of serum phospholipid and nonesterified fatty acid (NEFA) were determined. EPA levels in serum phospholipid and NEFA increased by 4.3- and 2.7-fold, respectively, in the seal oil supplemented group. DHA levels rose 1.5- and 2.1-fold, respectively, and DPA levels rose 0.5- and 0.7-fold, respectively. Arachidonic acid (AA) levels dropped by 26% in both serum phospholipid and serum NEFA. There was a significant decrease in the ratio of n-6 to n-3 fatty acids in serum phospholipid from 7.2 to 2.1 and a significant increase in the ratio of EPA/AA in NEFA. Ingestion of seal oil raised the coagulant inhibitor, protein C, values by 7% and decreased plasma fibrinogen by 18%. No alterations in other hemostatic variables, including plasma activity of Factors VII, VIII, IX, and X and antithrombin, or in the concentrations of von Willebrand Factor, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, Apo A-1, or lipoprotein(a) were observed in either group. Other risk factors for cardiovascular disease, including hematocrit, white blood cell count, plasma viscosity, systolic and diastolic blood pressures, heart rate, and platelet aggregation after stimulation with ADP or collagen did not change. Our results indicate that seal oil supplementation in healthy, normocholesterolemic subjects decreased the n-6/n-3 ratio and increased EPA, DHA, and DPA and the ratio of EPA/AA and DHA/AA in the serum phospholipid and NEFA, while exhibiting a modest beneficial effect on fibrinogen and protein C levels.

Adult↗
PubMed1999

TCR-mediated involvement of CD4+ transgenic T cells in spontaneous inflammatory bowel disease in lymphopenic mice.

Spontaneous colitis resembling ulcerative colitis developed in 3 of 10 independent TCR transgenic (Tg) mouse lines maintained under specific pathogen-free conditions. All three susceptible lines were CD4 lymphopenic, whereas resistant lines had normal numbers of CD4+ T cells. Thus, cytochrome c-specific 5C.C7 TCR Tg mice developed colitis only when crossed onto a SCID- or Rag-1-deficient background. A second line of lymphopenic cytochrome c-specific Tg mice bearing the AND TCR also developed colitis. In both cases, CD4+ T cells expressing the Tg-encoded TCR were preferentially activated in inflamed colons compared with lymph nodes or spleens. In contrast, Tg+CD4+ T cells remained quiescent in both inflamed and unaffected colons in another line of susceptible Tg mice carrying a TCR specific for myelin basic protein, suggesting a fortuitous cross-reactivity of the IEk-restricted cytochrome c-reactive AND and 5C.C7 TCRs with an Ag present in the gut. The percentage of CD4+ T cells expressing only endogenous TCR alpha-chains was increased consistently in inflamed colons in AND as well as 5C.C7 Rag-1-/- TCR Tg mice, suggesting that polyclonal CD4+ T cells were also involved in the pathogenesis of spontaneous colitis. Moreover, our data indicate that some alpha-chain rearrangement was still occurring in TCR Tg mice on a Rag-1-/- background, since activated CD4+ T cells expressing endogenously rearranged alpha-chains paired with the Tg-encoded beta-chain were detected consistently in the colons of such mice.

Adoptive Transfer↗
PubMed1999

Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB.

The tumor necrosis factor receptor 1 (TNFR1) and the Fas receptor recruit complexes formed by the interactions between RIP kinase, TRADD, FADD and RAIDD - adaptor proteins that contain death domains - which in turn recruit other proteins to initiate signaling [1][2][3][4][5]. To identify proteins associated with the TNF signaling pathway, we performed a yeast two-hybrid interaction screen using RIP as bait. We isolated a kinase, RIP3, which shares homology with the kinase domain of RIP and RIP2 (also known as Rick or CARDIAK). RIP3 could be co-immunoprecipitated with RIP, TRAF2 and TNFR1 in mammalian cells. The carboxy-terminal domain of RIP3, like that of RIP, could activate the transcription factor NFkappaB and induce apoptosis when expressed in mammalian cells. Interestingly, this region shares no significant sequence homology to the death domain of RIP, the caspase-recruiting domain (CARD) of RIP2 [6][7][8] or any other apoptosis-inducing domain. As with RIP and RIP2, the kinase domain of RIP3 was not required for either NFkappaB activation or apoptosis induction. Overexpression of a dominant-negative mutant of RIP3 strongly inhibited the caspase activation but not the NFkappaB activation induced by TNFalpha. Therefore, RIP3 appears to function as an intermediary in TNFalpha-induced apoptosis.

Apoptosis↗
PubMed1999

Mechanically evoked shortening of outer hair cells isolated from the guinea pig organ of Corti.

Outer hair cells isolated from the mammalian hearing organ have been shown to respond to mechanical stimuli at acoustic frequencies by expressing a change in cell length (e.g. Canlon et al., 1988). The acoustically evoked response is characterised by both a tonic length change following the envelope of the stimulus, and a frequency-dependent phasic component. We show here that mechanical stimulation at much lower frequencies directed at the cell body also elicits length changes of the outer hair cells. When the apical pole of isolated outer hair cells was compressed with a quartz fibre, a shortening or contraction at the basal pole was observed. Transverse indentation at the lateral membrane elicited shortenings at both ends of the cells. The sensitivity to the mechanical manipulation was changed by an altered tonicity of the external solution, or exposure to salicylate. As the response occurs at very low stimulus frequencies, it may account for the mechanism by which the hearing organ responds to the low frequency modulation component in complex signals like speech.

Animals↗
PubMed1999

Cytomegalovirus colitis in individuals without apparent cause of immunodeficiency.

Cytomegalovirus infection is usually reported in immunocompromised patients. In this study, apparently immunocompetent patients with cytomegaloviral colitis were reviewed. Records with a diagnosis of cytomegaloviral colitis from January 1989 to June 1996 were retrieved for analysis. Ten patients were included (median age 70 yr). The major presenting symptoms were diarrhea and hematochezia. Ulceration was the main macroscopic finding. Rectal bleeding was mostly self-limiting. Three patients developed local complications (rectovaginal fistula in two; rectal stricture in one). In the two patients with rectovaginal fistula, lymphocytes subsets and proliferative response were entirely normal. In the other patient, low B lymphocyte count and low response to mitogen were demonstrated. However, the immunoglobulins were not suppressed and rectal biopsies revealed noncaseating granulomas, suggesting activated cell-mediated immunity. In conclusion, a high index of suspicion is crucial for early diagnosis of cytomegaloviral colitis in patients with bloody diarrhea, even though obvious evidence of immunodeficiency is lacking.

Aged↗
PubMed1998

Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1.

The SH2- and SH3-containing adaptor molecules serve to recruit cytosolic signal-transducing molecules to the activated receptor tyrosine kinases. In this study, we report the molecular cloning of a novel adaptor-like protein, Grap-2 (Grb-2 related adaptor protein 2), using the multisubstrate docking protein Gab-1 as bait in the yeast two-hybrid system. Sequence analysis revealed that Grap-2 contains a SH3-SH2-SH3 structure that has a high degree of sequence homology to those of the Grb-2 and Grap adaptor molecules. However, unlike in Grap and Grb-2, the SH2 and the C-terminal SH3 domains of Grap-2 are separated by a 120-amino-acid glutamine-rich sequence that shows no apparent homology to any known molecule or structural motif. The C-terminal SH3 domain of Grap-2 alone is sufficient to bind to Gab-1. Furthermore, Northern blot analysis demonstrated that Grap-2 has two major transcripts of 1.4 and 4.0 kb that can only be detected in tissues rich in leukocytes and in two leukemia cell lines. This highly restricted pattern of expression suggests that Grap-2 may participate in leukocyte-specific protein tyrosine kinase signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Kinetics of activation of a Ca2+-dependent K+ current induced by flash photolysis of caged carbachol in isolated guinea-pig outer hair cells.

It has been shown that the application of acetylcholine activates a Ca2+-dependent K+ current in outer hair cells, and the resulting hyperpolarization is thought to be an important part of the inhibition mediated by cholinergic efferent nerve fibres to the cochlea. In order to study the kinetics of the current, flash photolysis has been used to apply a cholinergic agonist, carbachol, rapidly to isolated outer hair cells. A delay in the onset of the outward potassium current following photorelease of carbachol was consistently observed, and the activation phase of the response could be described by a sigmoidal-like function with a mean delay of 59 ms and time constant of 71 ms. The sum of these values lies within the time scale reported for the onset of the inhibition following electrical stimulation of the efferent nerves. Although a distinct current attributable to an acetylcholine receptor was not visible in these experiments, indirect evidence for a carbachol-induced influx of Ca2+ was obtained.

Animals↗
PubMed1998

Construction of a modular yeast two-hybrid cDNA library from human EST clones for the human genome protein linkage map.

Identification of all human protein-protein interactions will lead to a global human protein linkage map that will provide important information for functional genomics studies. The yeast two-hybrid system is a powerful molecular genetic approach for studying protein-protein interactions. To apply this technology to generate a human protein linkage map, the first step is to construct two-hybrid cDNA libraries that cover the entire human genome. With a homologous recombination-mediated approach, we have constructed a modular human EST-derived yeast two-hybrid library in the Gal4 activation domain-based vector, pACT2. Quality analysis of this library indicated that the approach of constructing two-hybrid cDNA libraries from individually arrayed human EST clones is feasible, and such a two-hybrid library is suitable for detecting protein-protein interactions. This is also the first time that a comprehensive two-hybrid system cDNA library has been constructed from a collection of individually arrayed EST clones.

Chromosome Mapping↗
PubMed1998

Axial and transverse stiffness measures of cochlear outer hair cells suggest a common mechanical basis.

The function of the hearing organ is based on mechanical processes occurring at the cellular level. The mechanical properties of guinea-pig isolated sensory cells were investigated using two different techniques. The stiffness of the outer hair cells along the longitudinal axis was measured by compressing the cell body using stiffness-calibrated quartz fibres. For cells with a mean length of 69 micron, the mean axial compression stiffness was 1. 1+/-0.8 mN/m (+/-SD). There was an inverse relation between stiffness and cell length. The stiffness of the cell membrane perpendicular to the longitudinal axis of the sensory cell was measured by indenting the cell membrane with a known force. The mean lateral indentation stiffness was 3.3+/-1.5 mN/m (+/-SD) for cells with a mean length of 64 microm. Longer cells were less stiff than short cells. Modelling the hair cell as a shell with bending resistance, finite element calculations demonstrated that the axial compression stiffness correlated well with the lateral indentation stiffness, and that a simple isotropic model is sufficient to explain the experimental observations despite the different stress strain states produced by the two techniques. The results imply that the two different stiffness properties may originate from the same cytoskeletal structures. It is suggested that the mechanical properties of the outer hair cells are designed to influence the sound-induced motion of the reticular lamina. In such a system, stiffness changes of the outer hair cell bodies could actively control the efficiency of the mechanical coupling between the basilar membrane and the important mechanoelectrical transduction sites at the surface of the hearing organ.

Animals↗
PubMed1998

Acoustic trauma causes reversible stiffness changes in auditory sensory cells.

A common cause of hearing impairment is exposure to loud noise. Recent research has demonstrated that the auditory mechanosensory cells are essential for normal hearing sensitivity and frequency selectivity. However, little is known about the effect of noise exposure on the mechanical properties of the auditory sensory cells. Here we report a significant reduction in the stiffness and cell length of the outer hair cells after impulse noise exposure, suggesting that mechanical changes at the cellular level are involved in noise-induced hearing loss. There is a recovery of the cellular stiffness and cell length over a two-week period, indicating an activation of cellular repair mechanisms for restoring the auditory function following noise trauma. The reduced stiffness observed at the cellular level is likely to be the cause for the downward shift of the characteristic frequency seen following acoustic trauma. The deterioration and the recovery of the mechanical properties of outer hair cells may form important underlying factors in all kinds of noise-induced hearing loss.

Animals↗
PubMed1998

Accuracy of repeated blood sampling in rats: a new technique applied in pharmacokinetic/pharmacodynamic studies of the interaction between warfarin and co-enzyme Q10.

In the past, combined pharmacokinetic/pharmacodynamic (PK/PD) modeling studies of oral anticoagulants in rats have been hampered by the technical problems of blood sampling. In the present study, a semi-micromethod of preparing serial plasma samples for accurate assessment of the prothrombin times (PT) and clotting factor VII activity (CFA) in rats is proposed. The method consists of orbital bleeding, blood sample weighing, gravity calculation and buffer volume adjustment. No significant differences of CFA (percentage normal) were found between citrate-diluted and undiluted plasma. This technique was employed to examine the possibility of PK/PD interaction between warfarin and Co-enzyme Q10 (CoQ10). Rats were given a single oral dose (1.5 mg/kg) of warfarin either alone or on day 4 of an 8-day oral dosing regimen of 10 mg/kg CoQ10 daily. Serial plasma and serum samples, which were subjected to respectively measurements of the anticoagulant effects and concentrations of warfarin and its main metabolites, were obtained over a 96-h period following warfarin administration. All rats survived the whole experiment and maintained a stable condition except for a marked hematocrit decrease. CoQ10 significantly augmented warfarin metabolism but showed little effect on the absorption of warfarin. CoQ10 alone had no apparent effect on either the PT or CFA. The concomitant administration of CoQ10 and warfarin does not significantly affect the anticoagulant effect of warfarin. In conclusion, the proposed serial orbital bleeding technique in rats to prepare an accurate citrate-diluted plasma for PT and CFA measurement is rapid and reliable.

Animals↗