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C K Botz

Publications and source records attributed to C K Botz.

13 recordsLinked to original sources

Blood glucose regulation using closed- and open-loop insulin delivery systems. II. Peripheral primed square wave infusions.

Glucose was infused into anaesthetized dogs before and after pancreatectomy. In the diabetics blood glucose was regulated first by closed-loop and then by open-loop insulin delivery schemes. Insulin requirements for the latter were determined by resolving the former into a sequence of 3 different infusion rates: during the baseline and recovery periods, basal insulin was delivered at 0.37 +/- 0.02 mU/kg/min, while during the 60 min glucose infusion (10 mg/kg/min) there was an 8 min infusion at 4.96 +/- 0.37 mU/kg/min and a 52 min component at 1.85 +/- 0.08 mU/kg/min. With the open-loop method under these highly standardized conditions glycaemia was similar to normal controls but IRI levels were significantly higher, 13.5 vs 8.0 microU/ml (p less than 0.05) in the baseline and recovery periods and 74 vs 25 microU/ml (p less than 0.05) during the glucose infusion. It was concluded that: constant normoglycaemia can be maintained in the basal state by a constant rate of peripheral insulin delivery but at rates resulting in peripheral hyperinsulinaemia; the glycaemic response to glucose infusion can be normalized by a two component waveform of insulin delivery; and the closed-loop method can serve as a useful guide in determining insulin requirements.

Animals

Blood glucose regulation using an open-loop insulin delivery system in pancreatectomized dogs given glucose infusions. I. Portal square waves.

This study characterizes the glycaemic and insulin responses of a group of 5 anaesthetized dogs to a portal glucose infusion of 10 mg/kg/min before and after pancreatectomy. Insulin was administered intraportally to the pancreatectomized dogs according to a simple preprogrammed waveform composed of a constant basal rate of 0.35 +/- 0.02 mU/kg/min which was increased to 2.00 mU/kg/min at the time of the 60 minute glucose challenge. When this square waveform was applied the glycaemic response was similar to that seen in the normal controls in the baseline and challenge periods. Blood glucose concentration differed significantly (p less than 0.05) only from 20 to 100 minutes after the end of the challenge when it was higher by 20 +/- 1 mg/dl. Insulin levels were not significantly different from controls. It may be concluded that normoglycaemia and normoinsulinaemia can be maintained by a simple constant rate of portal insulin delivery while the blood glucose response to a glucose infusion can be ostensibly normalized without hyperinsulinaemia simply by enhancing insulin delivery during the challenge. The feasibility of this approach implies that with further development of the preprogrammed waveforms and with a greater understanding of their characteristics portable insulin delivery systems may be realized which accomodate more physiological challenges. The portal route for insulin delivery may however be necessary if peripheral hyperinsulinism is inappropriate.

Animals

An improved technique for the rapid continuous measurement of whole blood glucose, suitable for clinical application in an artificial endocrine pancreas.

An improved bedside technique for the continuous monitoring of glycemia is described. A linear relationship results between whole blood glucose concentration and plasma glucose levels, and allows the calibration of the system in terms of plasma glucose levels. In operation venous blood is withdrawn at a steady rate using a double-lumen catheter and directed to a continuous-flow laboratory analyzer, where glucose analysis is carried out using a modified glucose oxidase-peroxidase methodology. The improvements in this technique include: i) a reduction in the delay of the analyzer to 90 s, making it suitable for application in a system for blood glucose regulation, ii) a minimal blood requirement of 3 ml/h, permitting long-term monitoring, iii) elimination of the need for systemic anticoagulation, iv) an excellent correlation (r = 0.993) between the measured whole blood glucose and the actual plasma glucose concentration, v) an average baseline drift of +0.5 mg%/h, vi) a sensitivity loss of less than 0.1%/h, and vii) a reasonable operating cost. This technique was implemented as part of a clinical apparatus known as an artificial endocrine pancreas which has been reliably applied in clinical and animal studies.

Adult

Studies with an artificial endocrine pancreas.

Short-term studies with an artificial endocrine pancreas have provided insights into the pathophysiology of diabetes and demonstrated the ability of such a system to restore and maintain glucose homeostasis in human subjects given either their usual diet, a 50 gm oral glucose tolerance test, or a moderate level of physical exercise. Animals were used to demonstrate that a peripheral route of insulin delivery by the artificial pancreas is equivalent to the portal route.

Animals

Comparison of peripheral and portal routes of insulin infusion by a computer-controlled insulin infusion system (artificial endocrine pancreas).

This study was undertaken to determine the different consequences of portal and peripheral routes of insulin administration by the artificial endocrine pancreas. Intraportal glucose was infused (10 mg./min./kg. for 60 minutes) in anesthetized normal and pancreatectomized dogs while blood glucose concentrations were monitored continuously. During computer-controlled insulin administration normal glucose tolerance was restored by both portal and peripheral routes of insulin delivery. There were also no significant differences in (1) glycemic patterns, (2) insulin infusion patterns, (3) peripheral IRI levels, and (4) total insulin requirements between the two routes. It is apparent that the peripheral route, which is more readily accessible than the portal route, may be an appropriate infusion site for an implantable or portable prosthesis for controlling blood glucose concentration.

Animals

An all-plastic double-lumen catheter for continuous blood sampling.

The all-plastic double-lumen catheter described in this paper represents a significant improvement over previously reported catheters. It is used routinely for continuous blood withdrawal in two clinical investigation units and one experimental laboratory in Toronto. No experiments have been terminated due to catheter failure or clot formation and no maximum time limit of its use has been established. In clinical use with adult patients (4), the outer cannula has been kept open overnight with a slow saline drip after 18 hours of use. The same cannula has then been reused the next day for another 16 hours with a new adapter precut to size. Its design enzures that: (1) heparin is mixed with the blood at the site of blood sampling. (2) Blood is never brought into contact with glass or metal. (3) The blood channel is a uniform polyethylene tube with no discontinuities and no junctions, except where it is introduced into the peristaltic pump tube. The overall manufacturing process is simple, and percutaneous insertion is straightforward. Through its use, clotting in the blood withdrawal line and thrombus formations in the blood analyzer are no longer problems to limit the use of techniques requiring continuous blood withdrawal.

Blood Specimen Collection