The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access... more The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access failure, at consid-An international hemodialysis study. The Dialysis Outcomes erable expense and morbidity. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, longituand Practice Patterns Study (DOPPS) is a prospective,
The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access... more The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access failure, at consid-An international hemodialysis study. The Dialysis Outcomes erable expense and morbidity. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, longituand Practice Patterns Study (DOPPS) is a prospective,
Background. Optimal waiting time before first use of vascular access is not known. Methods. Two p... more Background. Optimal waiting time before first use of vascular access is not known. Methods. Two practices-first cannulation time for fistulae and grafts, and blood flow rate-were examined as potential predictors of vascular access failure in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Access failure (defined as time to first failure or first salvage intervention) was modelled using Cox regression. Results. Among 309 haemodialysis facilities, 2730 grafts and 2154 fistulae were studied. For grafts, first cannulation typically occurred within 2-4 weeks at 62% of US, 61% of European and 42% of Japanese facilities. For fistulae, first cannulation occurred <2 months after placement in 36% of US, 79% of European and 98% of Japanese facilities. Overall, the relative risk (RR) of graft failure in Europe was lower compared with the USA (RR ¼ 0.69, P ¼ 0.04). The RR of graft failure (reference group ¼ first cannulation at 2-3 weeks) was 0.84 with first cannulation at <2 weeks (P ¼ 0.11), 0.94 with first cannulation at 3-4 weeks (P ¼ 0.48) and 0.93 with first cannulation at >4 weeks (P ¼ 0.48). The RR of fistula failure was 0.72 with first cannulation at <4 weeks (P ¼ 0.08), 0.91 at 2-3 months (P ¼ 0.43) and 0.87 at >3 months (P ¼ 0.31) (reference group ¼ first cannulation at 1-2 months). Facility median blood flow rate was not a significant predictor of access failure.
The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access... more The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access failure, at consid-An international hemodialysis study. The Dialysis Outcomes erable expense and morbidity. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, longituand Practice Patterns Study (DOPPS) is a prospective,
Background The incidence of human immunodeficiency virus (HIV) infection is rising, and as a resu... more Background The incidence of human immunodeficiency virus (HIV) infection is rising, and as a result, tuberculosis (TB) has become a resurgent problem in many developed countries. Objectives The aim of this study was to review the spectrum of abdominal TB and its surgical management in our institution. Methods A retrospective review of all abdominal TB cases notified to the health authorities by our institution from Jan 01 to Oct 07 was performed. Results There were 57 patients (37 men) with abdominal TB, with a median age of 47 (range 14–74) years. Active pulmonary TB was present in 27 patients (47%). Positive HIV status was present in 30% and untested in 58%. The majority of patients underwent computed tomography scans (n = 50, 88%). The main radiological findings included bowel thickening, lymphadenopathy, ascites, free gas suggestive of perforation, and abscesses. The diagnosis of TB was confirmed on microbiological and/or histological examination in 72%, while the remaining 28% were diagnosed based on the clinical presentation and radiological imaging. All patients were commenced on anti-tuberculous therapy. TB involved the small or large bowel in 33 patients, mesenteric lymphadenopathy in 24, peritoneum in 13, spleen in seven, pancreas in two, anus in two, and the liver in two. Disseminated (including pulmonary) TB occurred in 27 patients (47%), while isolated intra-abdominal TB occurred in the remaining 30 patients (53%). Twenty-five patients (44%) underwent surgery—16 laparotomies (six perforated viscus, five intestinal obstruction, three suspected malignancies, and two for suspected acute abdomen), five laparoscopic procedures (four diagnostic, one gastrojejunostomy bypass for gastric outlet obstruction), two appendicectomies, one drainage of abscess, and one anal fistulotomy. Conclusions Although TB is eminently treatable medically, surgery is still often required for suspected or confirmed abdominal TB presenting with acute complications or as atypical diagnostic problems. The role of laparoscopy is likely to be more significant in future in the management of abdominal TB.
Susceptibility of methionine residues to oxidation is a significant issue of protein therapeutics... more Susceptibility of methionine residues to oxidation is a significant issue of protein therapeutics. Methionine oxidation may limit the product's clinical efficacy or stability. We have studied kinetics of methionine oxidation in the Fc portion of the human IgG2 and its impact on the interaction with FcRn and Protein A. Our results confirm previously published observations for IgG1 that two analogous solvent-exposed methionine residues in IgG2, Met 252 and Met 428, oxidize more readily than the other methionine residue, Met 358, which is buried inside the Fc. Met 397, which is not present in IgG1 but in IgG2, oxidizes at similar rate as Met 358. Oxidation of two labile methionines, Met 252 and Met 428, weakens the binding of the intact antibody with Protein A and FcRn, two natural protein binding partners. Both of these binding partners share the same binding site on the Fc. Additionally, our results shows that Protein A may serve as a convenient and inexpensive surrogate for FcRn binding measurements.
The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access... more The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access failure, at consid-An international hemodialysis study. The Dialysis Outcomes erable expense and morbidity. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, longituand Practice Patterns Study (DOPPS) is a prospective,
The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access... more The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access failure, at consid-An international hemodialysis study. The Dialysis Outcomes erable expense and morbidity. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, longituand Practice Patterns Study (DOPPS) is a prospective,
Background. Optimal waiting time before first use of vascular access is not known. Methods. Two p... more Background. Optimal waiting time before first use of vascular access is not known. Methods. Two practices-first cannulation time for fistulae and grafts, and blood flow rate-were examined as potential predictors of vascular access failure in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Access failure (defined as time to first failure or first salvage intervention) was modelled using Cox regression. Results. Among 309 haemodialysis facilities, 2730 grafts and 2154 fistulae were studied. For grafts, first cannulation typically occurred within 2-4 weeks at 62% of US, 61% of European and 42% of Japanese facilities. For fistulae, first cannulation occurred <2 months after placement in 36% of US, 79% of European and 98% of Japanese facilities. Overall, the relative risk (RR) of graft failure in Europe was lower compared with the USA (RR ¼ 0.69, P ¼ 0.04). The RR of graft failure (reference group ¼ first cannulation at 2-3 weeks) was 0.84 with first cannulation at <2 weeks (P ¼ 0.11), 0.94 with first cannulation at 3-4 weeks (P ¼ 0.48) and 0.93 with first cannulation at >4 weeks (P ¼ 0.48). The RR of fistula failure was 0.72 with first cannulation at <4 weeks (P ¼ 0.08), 0.91 at 2-3 months (P ¼ 0.43) and 0.87 at >3 months (P ¼ 0.31) (reference group ¼ first cannulation at 1-2 months). Facility median blood flow rate was not a significant predictor of access failure.
The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access... more The Dialysis Outcomes and Practice Patterns Study (DOPPS): complications, such as vascular access failure, at consid-An international hemodialysis study. The Dialysis Outcomes erable expense and morbidity. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, longituand Practice Patterns Study (DOPPS) is a prospective,
Background The incidence of human immunodeficiency virus (HIV) infection is rising, and as a resu... more Background The incidence of human immunodeficiency virus (HIV) infection is rising, and as a result, tuberculosis (TB) has become a resurgent problem in many developed countries. Objectives The aim of this study was to review the spectrum of abdominal TB and its surgical management in our institution. Methods A retrospective review of all abdominal TB cases notified to the health authorities by our institution from Jan 01 to Oct 07 was performed. Results There were 57 patients (37 men) with abdominal TB, with a median age of 47 (range 14–74) years. Active pulmonary TB was present in 27 patients (47%). Positive HIV status was present in 30% and untested in 58%. The majority of patients underwent computed tomography scans (n = 50, 88%). The main radiological findings included bowel thickening, lymphadenopathy, ascites, free gas suggestive of perforation, and abscesses. The diagnosis of TB was confirmed on microbiological and/or histological examination in 72%, while the remaining 28% were diagnosed based on the clinical presentation and radiological imaging. All patients were commenced on anti-tuberculous therapy. TB involved the small or large bowel in 33 patients, mesenteric lymphadenopathy in 24, peritoneum in 13, spleen in seven, pancreas in two, anus in two, and the liver in two. Disseminated (including pulmonary) TB occurred in 27 patients (47%), while isolated intra-abdominal TB occurred in the remaining 30 patients (53%). Twenty-five patients (44%) underwent surgery—16 laparotomies (six perforated viscus, five intestinal obstruction, three suspected malignancies, and two for suspected acute abdomen), five laparoscopic procedures (four diagnostic, one gastrojejunostomy bypass for gastric outlet obstruction), two appendicectomies, one drainage of abscess, and one anal fistulotomy. Conclusions Although TB is eminently treatable medically, surgery is still often required for suspected or confirmed abdominal TB presenting with acute complications or as atypical diagnostic problems. The role of laparoscopy is likely to be more significant in future in the management of abdominal TB.
Susceptibility of methionine residues to oxidation is a significant issue of protein therapeutics... more Susceptibility of methionine residues to oxidation is a significant issue of protein therapeutics. Methionine oxidation may limit the product's clinical efficacy or stability. We have studied kinetics of methionine oxidation in the Fc portion of the human IgG2 and its impact on the interaction with FcRn and Protein A. Our results confirm previously published observations for IgG1 that two analogous solvent-exposed methionine residues in IgG2, Met 252 and Met 428, oxidize more readily than the other methionine residue, Met 358, which is buried inside the Fc. Met 397, which is not present in IgG1 but in IgG2, oxidizes at similar rate as Met 358. Oxidation of two labile methionines, Met 252 and Met 428, weakens the binding of the intact antibody with Protein A and FcRn, two natural protein binding partners. Both of these binding partners share the same binding site on the Fc. Additionally, our results shows that Protein A may serve as a convenient and inexpensive surrogate for FcRn binding measurements.
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Papers by Kenneth Chen