Improved adhesion and proliferation of human endothelial cells on polyethylene precoated with monoclonal antibodies directed against cell membrane antigens and extracellular matrix proteins.

Endothelial cell seeding may improve the patency of synthetic vascular grafts provided that platelet reactivity of nonendothelialized sites is not increased. We have investigated if surface-adsorbed monoclonal antibodies directed against endothelial cell membrane proteins and against extracellular matrix proteins promote the adhesion and proliferation of cultured human endothelial cells, without causing platelet deposition at non-endothelialized sites. Adhesion of endothelial cells onto polyethylene coated with monoclonal antibodies directed against endothelial cell-specific membrane antigens, integrin receptors and glycoprotein CD31 was equal to or higher than adhesion onto fibronectin-coated polyethylene. Endothelial cells did not proliferate on these surface-adsorbed antibodies. However, pre-coating of polyethylene with mixtures of endothelial cell-specific monoclonal antibodies and monoclonal antibodies directed against fibronectin or von Willebrand factor, resulted in relatively high adhesion and optimal proliferation. Platelet reactivity of the polyethylene surface was found to significantly increase after adsorption of fibronectin, endothelial cell-specific monoclonal antibody or its Fc fragments. In contrast, adsorption of F(ab')2 fragments of endothelial cell-specific monoclonal antibody did not promote platelet deposition. Therefore, it is concluded that coating of vascular graft materials with mixtures of F(ab')2 fragments of monoclonal antibodies specifically directed against endothelial cells and against extracellular matrix proteins may be an effective way to both promote the growth of seeded endothelial cells and limit platelet-graft interaction.     

Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled leukotriene b4 antagonist.

Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. METHODS: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. RESULTS: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate.     

Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer

PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25–71) years and a rectal tumor at a mean of 3 (range, 0–5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1–8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean follow-up of 24 (range, 1–60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n=2) and incontinence (n=3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 35 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1–5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0–30) minutes. CONCLUSION: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome. Supported by the Profileringsfonds of the Maastricht University Hospital, The Netherlands, and by the Stichting Fondsenwervingsactie Volksgezondheid, Amsterdam, The Netherlands. Read in part at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1995.     

Differences in aerodynamic characteristics of new and dysfunctional Provox®2 voice prostheses in vivo

Tracheoesophageal voice prostheses need to be replaced due to increased airflow resistance or retrograde leakage of fluid into the trachea as a consequence of biofilm formation. Previous in vitro studies show a change of aerodynamic features of biofilm covered voice prostheses after removal of the prostheses out of the patient. To assess these changes in an in situ situation, aerodynamic characteristics were measured within 45 patients at the beginning and at the end of the wearing process of the Provox 2 voice prosthesis. As a consequence, the influence of biofilm formation on aerodynamic characteristics can be evaluated. In the majority of cases, leakage through the prosthesis was the reason for replacement. No differences were found in the total flow, volume range and intratracheal pressure (ITP) of the voice prostheses measured. The airflow resistance of biofilm covered prostheses was significantly reduced compared to new clean prostheses. However, no correlation was found between the extent of biofilm and the different aerodynamic features measured. Biofilm formation on the Provox 2 is responsible for both reduction in airflow resistance and leakage through the prosthesis by deterioration of the silicone rubber material.