Biomedical subjects

Matthew J Quinn

Publications and source records attributed to Matthew J Quinn.

7 recordsLinked to original sources

PubMed2007

Passivating protein coatings for implantable glucose sensors: evaluation of protein retention.

The long-term function of implantable biosensors is limited by the foreign-body reaction (FBR). Since the acute phase of the FBR involves macrophage attachment mediated by adsorbed fibrinogen, preadsorption, and retention of other proteins might reduce the FBR. The retention of preadsorbed albumin, hemoglobin, von Willebrand's factor, and high-molecular-weight kininogen was therefore measured after exposure to plasma. The retention of preadsorbed proteins after incubation with monocyte cultures and implantation in rats was also measured. Fibrinogen adsorption from plasma to the preadsorbed surfaces was also measured. Hemoglobin adsorption was higher than that for other proteins, and it also had the greatest retention after exposure to blood plasma. When surfaces preadsorbed with hemoglobin were incubated with monocytes, more of the hemoglobin was displaced than that after incubation in plasma, while still more hemoglobin was displaced when the surfaces were implanted in vivo. Protein preadsorption on polystyrene greatly reduced fibrinogen adsorption. However, polyurethane surfaces used for glucose sensors had low fibrinogen adsorption compared with polystyrene, and this low level was not further reduced by preadsorption with other proteins. Preadsorbed proteins on polymers appear to be removed by passive exchange and/or displacement by plasma proteins and by proteases released by monocytes.

Absorbable Implants↗

PubMed2005

An implantable subcutaneous glucose sensor array in ketosis-prone rats: closed loop glycemic control.

A closed loop system of diabetes control would minimize hyperglycemia and hypoglycemia. We therefore implanted and tested a subcutaneous amperometric glucose sensor array in alloxan-diabetic rats. Each array employed four sensing units, the outputs of which were processed in real time to yield a unified signal. We utilized a gain-scheduled insulin control algorithm which rapidly reduced insulin delivery as glucose concentration declined. Such a system was generally effective in controlling glycemia and the degree of lag between blood glucose and the sensor signal was usually 3-8 min. After prolonged implantation, this lag was sometimes longer, which led to impairment of sensor accuracy. Using a prospective two-point calibration method, sensor accuracy and closed loop control were good. A revised algorithm yielded better glycemic control than the initial algorithm did. Future research needs to further improve calibration methods and reduce foreign body fibrosis in order to avoid a time-related increase in lag duration.

Algorithms↗

PubMed2005

A novel insulin delivery algorithm in rats with type 1 diabetes: the fading memory proportional-derivative method.

An algorithm designed to automatically control insulin delivery was tested in rats with Type 1 diabetes. This nonlinear algorithm included a fading memory component of proportional and derivative errors in order to simulate normal insulin secretion. Error-weighting functions for the proportional and derivative terms were used with a performance index designed for error adaptation. In the first version of the algorithm, the proportional gain was adaptively varied. In the second version, a low rate of basal insulin delivery was adaptively varied. Six 6-h studies with each version were conducted using frequent blood sampling and intravenous insulin delivery. In Version 2 studies, blood glucose levels during the last two hours were well-controlled and significantly lower than in Version 1 (118 +/- 2.0 vs. 130 +/- 2.9 mg/dL). Neither version produced hypoglycemia. Future research using this algorithm needs to focus on automated glucose sensing in combination with insulin delivery.

Algorithms↗

PubMed2004

The effect of local subcutaneous delivery of vascular endothelial growth factor on the function of a chronically implanted amperometric glucose sensor.

The foreign body capsule that forms around implanted devices such as glucose sensors is hypovascular and has limited permeability to glucose. Such a capsule may function better if well vascularized. We hypothesized that capsular vascularization achieved by local release of vascular endothelial growth factor (VEGF) would lead to enhanced function. Amperometric glucose sensor array disks, each with four indicating electrodes, were implanted into rats. Animals received local subcutaneous infusions of VEGF(165) via osmotic pumps at a location on the sensor face 2 mm from one of the electrodes ("near units"). "Intermediate" electrode units were 15 mm, and "distant" units were 22 mm, from the VEGF source. Every 2 weeks, a glucose infusion was given to assess sensor function by telemetry. Near units demonstrated a lower lag duration (delay after blood glucose) than intermediate and distant units. The mean absolute relative difference for near units was less than for distant units. The percentage of data pairs in the A region of the Clarke error grid of the near sensing units was greater than that of the distant units. Values for the functional measures for saline controls fell between near and distant VEGF values. Glucose sensor function was found to be more favorable in units immediately adjacent to the VEGF infusion port. The most likely cause for this finding is increased neovessel growth in the surrounding foreign body capsule. Slow release of angiogenic growth factors may be a potential method for chronically enhancing the function of a subcutaneously implanted biosensor.

Animals↗

PubMed2004

Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment.

Uncertainties have existed regarding the systematic induction and management of drug-induced diabetes mellitus (DM). Issues have included the optimal route of administration of the drug, methods of reducing drug toxicosis and mortality, how to induce type-1 versus type-2 DM, and how to manage labile DM in rats. In attempting to induce type-1 DM in Sprague-Dawley rats, we classified hyperglycemic animals as having type-1 DM only if their post-treatment blood ketone concentration was high. We found that multiple doses of alloxan led to significantly higher mortality than did a single dose. A single high dose (200 mg/kg of body weight given intraperitoneally) was the best treatment and led to 70% incidence of type-1 DM and only 10% mortality. In contrast, intravenous administration of similar doses was toxic. Assiduous management of alloxan-induced DM is crucial to avoid severe hypoglycemia from massive insulin release and to avoid diabetic ketoacidosis. Frequent glucose monitoring and appropriate administration of carbohydrate and fluids is necessary during this stage. For long-term management, daily administration of long-acting insulin (glargine) appears to be safe and effective. Rapid-acting insulins reduce glucose concentration rapidly, and must be used with caution. If specific precautions are observed, intraperitoneal administration of high-dose alloxan to laboratory rats leads to a condition that closely resembles human type-1 DM.

Alloxan↗

PubMed2003

Vascularizing the tissue surrounding a model biosensor: how localized is the effect of a subcutaneous infusion of vascular endothelial growth factor (VEGF)?

Implantable continuous biosensors would improve disease management but long term function of such devices have been limited by a hypovascular foreign body capsule that inhibits influx of analytes. To assess whether capsule vascularity could be increased, we studied the histologic effects of a 28-day continuous infusion of vascular endothelial growth factor (VEGF) (0.45 microg/day) vs. saline from the surface of a model disk biosensor that was implanted subcutaneously in rats. At day 40, tissue was obtained at varying distances from the infusion port and capsular microvessels were counted using two histologic techniques. VEGF treatment led to a marked increase in capillary density. In tissue located 1 mm away from the infusion site, capillary density in VEGF-treated animals was 200-300% higher than in saline controls. Tissue located 13 mm away, but not 25 mm away, also demonstrated neovascularization. Serum obtained from a distant vein during the infusion did not show an elevated concentration of VEGF. These data demonstrate that a subcutaneous infusion of VEGF creates localized neovascularization of the foreign body capsule and suggest that systemic effects of VEGF are avoidable. Vascularization of a foreign body capsule surrounding a subcutaneous biosensor might well extend its useful life.

Animals↗

PubMed2003

A fully implantable subcutaneous glucose sensor array: enhanced accuracy from multiple sensing units and a median-based algorithm.

Although continuous electrochemical glucose monitoring holds promise in the management of diabetes, its utility is limited in part because of error of unclear origin. The use of redundant glucose sensors in an array might reduce such error. We hypothesized that in a subcutaneously implanted array, a median-based continuous computation that excludes outlying data would lead to more accurate glucose measurement than averaging of all signals. Each rat was implanted with an array of four sensing units, and each unit transmitted data independently to an external monitoring device. Animals underwent perturbation of glucose by insulin infusions in diabetic animals and glucose infusions in nondiabetic animals, and in both, capillary glucose monitoring was performed frequently. Repeat glucose perturbation studies were performed every 1-2 weeks. We observed that a median-based technique, the Z-score with Median Absolute Deviation (ZMAD), consistently led to greater sensing accuracy as compared with signal averaging. The ZMAD technique yielded a correlation coefficient of 0.93, and 96% of values fell in the A and B regions of the Clarke error grid, demonstrating a high degree of accuracy of the unified signal. When tested in an implanted array of glucose sensors, a median-based technique (ZMAD) yields an accurate unified signal, and its accuracy is superior to signal averaging.

Algorithms↗