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D G Covell

Publications and source records attributed to D G Covell.

67 records · Page 4Linked to original sources
PubMed1985

Information needs in office practice: are they being met?

We studied the self-reported information needs of 47 physicians during a half day of typical office practice. The physicians raised 269 questions about patient management. Questions related to all medical specialties and were highly specific to the individual patient's problem. Subspecialists most frequently asked questions related to other subspecialties. Only 30% of physicians' information needs were met during the patient visit, usually by another physician or other health professional. Reasons print sources were not used included the age of textbooks in the office, poor organization of journal articles, inadequate indexing of books and drug information sources, lack of knowledge of an appropriate source, and the time required to find the desired information. Better methods are needed to provide answers to questions that arise in office practice.

Adult↗
PubMed1984

Pharmacokinetics of 5-fluorouracil following different routes of intrahepatic administration in the canine model.

In an effort to achieve high concentrations of 5-fluorouracil (5-FUra) in the hepatic circulation while minimizing systemic exposure, several routes of intrahepatic administration were compared in the canine model. To ascertain these data, 5-FUra (30 mg/kg) was given as a bolus into either a systemic vein (femoral vein), hepatic artery, hepatic artery distal to its ligation after hepatic dearterialization, or through the portal vein. Three dogs were studied for each route with concomitant blood samples taken from the inferior vena cava and hepatic vein at 1, 2, 3, 5, 10, 15, 30, and 60 min after injection. 5-FUra levels were determined in plasma by high-pressure liquid chromatography. Blood flow in the portal vein and hepatic artery was measured by an electromagnetic flowmeter. The data were best described by a multicompartmental model including the measured flows. Hepatic components of the model were separate arterial and portal compartments, with elimination from each described by linear kinetics. Analysis of the results indicated that the highest hepatic levels with the least systemic exposure, as indicated by drug levels in hepatic and peripheral vein, were realized following hepatic artery administration distal to its ligation after hepatic dearterialization.

Animals↗
PubMed1984

Monoclonal antitumor antibodies in the lymphatics.

Monoclonal antitumor antibodies are being administered iv in a number of medical centers for diagnosis or therapy of human cancers. However, when the objective is to detect or to treat tumor in regional lymph nodes, sc injection may prove more effective. After sc injection, monoclonal antibodies enter local lymphatic capillaries, pass to the draining lymph nodes, and bind to target cells there. Antibody not bound in the first node group encountered passes to more distant nodes. If still not removed from the lymph flow, antibody passes into the bloodstream, principally through the thoracic duct. Initial studies of the lymphatic approach were done with antibodies directed against antigens on normal cell types in the mouse lymph node. The use of antibodies to normal cells made it possible to study the pharmacokinetics of delivery in a reproducible, quantitatively interpretable system. The pharmacologic models developed were then applied to the design of experiments on line 10 hepatocarcinoma of guinea pigs. As little as 2 mg of line 10 tumor could be identified by gamma camera imaging in regional nodes after injection of 125I-labeled antibody. The uptake was immunologically specific, and autoradiography showed localization exclusively within the metastatic tumor. When the aim is to diagnose or treat early tumor metastases in the nodes, the lymphatic route can be expected to provide higher sensitivity, lower background, lower systemic toxicity, and faster localization than the iv route. Perhaps most interesting, the lymphatic route minimizes exposure of antibody to cross-reactive antigen present on normal tissues elsewhere in the body. Antitumor antibodies rejected for iv use because they also bind to normal tissues may, therefore, be useful in the diagnosis and treatment of lymph node metastases.

Animals↗
PubMed1984

Changes in the pharmacology of warfarin during long-term administration in dogs.

Patients receiving an apparently appropriate maintenance dosage of oral anticoagulant may show unexpected changes in clotting status without readily identifiable cause. The object of this study was to determine whether a consistent change in the pharmacology of warfarin could account for the clinical observations during long-term dosing. Eleven healthy adult dogs received constant daily oral doses of warfarin for 4 weeks. Plasma warfarin concentration (W), measured by gas chromatography, and prothrombin time (PT), measured by the one-stage assay of Quick, were determined daily. W and PT decreased significantly (p less than 0.05) during the last 2 weeks of long-term treatment. No pharmacodynamic changes were observed after prolonged warfarin treatment, suggesting that the decreases in PT were due solely to the decreased W. The decrease in W was not due to an increased free warfarin fraction or to a reduction in W absorption from the gut. The reproducibility of these results was demonstrated in a second group of experiments done 1 month after the first set of studies. Over the entire group of dogs there was no consistent change in warfarin clearance during prolonged dosing. We conclude that during constant daily dosing, W and PT reach early peak values, after which they decrease to levels significantly below peak levels. These results suggest that clinical anticoagulation may require multiple dosage adjustments despite the early attainment of apparently therapeutic anticoagulant regulation with a fixed dosage schedule.

Animals↗
PubMed1983

Monoclonal antibodies in the lymphatics: selective delivery to lymph node metastases of a solid tumor.

After subcutaneous injection, monoclonal antibodies directed against a tumor can enter local lymphatic vessels, pass to the draining lymph nodes, and bind to metastases there. Lymphatic delivery of antibody to early metastases is more efficient than intravenous administration, and the lymphatic route can be used to image smaller metastatic deposits. Perhaps more important, the lymphatic route minimizes binding of antibodies to circulating tumor antigens and to cross-reactive antigens present on normal tissues. Antibodies inappropriate for intravenous use because of binding to normal tissues may therefore be useful against lymph node metastases when injected subcutaneously or directly into lymphatic vessels.

Animals↗
PubMed1983

The effect of hepatic uptake on the disappearance of warfarin from the plasma of rats: a kinetic analysis.

To quantify the effects of the liver on the dose dependence of plasma warfarin clearance, an equal number of normal and functionally hepatectomized rats received an intravenous bolus of either 0.01, 0.1, or 1.0 mg/kg body weight of radiolabelled sodium warfarin. Serial samples of plasma and bile collected from each rat during the 1 hr experiment and of hepatic tissue collected at the end of the experiment were analyzed for radioactivity. The disappearance of warfarin from the plasma of hepatectomized rats was not dose dependent and suggested that the apparent dose dependency of plasma warfarin clearance is primarily the result of warfarin's interaction with hepatic tissue. The disappearance of warfarin from the plasma of normal rats was dose dependent with higher doses being cleared less rapidly. This dose dependence, however, was not reflected in the rate of biliary excretion of warfarin's metabolites, which did not show saturation over this dosage range. These results were used to develop a multicompartmental model of warfarin's pharmacokinetics. Plasma warfarin data collected from the hepatectomized rats were used to develop the extrahepatic components of the model, which was then expanded to include hepatic tissues based on data collected from normal rats. To simultaneously fit the plasma, biliary, and hepatic data required that at least two classes of hepatic tissue exchange warfarin with plasma. One tissue exhibited Michaelis-Menten saturation kinetics with Kd and maximum capacity estimated at 1.49E - 3 micrograms/ml and 2.72 micrograms/ml, respectively. The second class exhibited linear exchange kinetics with free plasma warfarin. Warfarin's association with the second class of hepatic tissue leads to its metabolic elimination. Consistent with our experimental findings, the rate of warfarin elimination from the plasma into the bile was linearly related to plasma warfarin concentration. Thus the single hepatic exchange nonlinearly was necessary and sufficient to account for the apparent dose dependency in plasma warfarin's pharmacokinetics. These results suggest that over the range of doses studied, the apparent dose dependent differences in the plasma warfarin concentration profile can be accounted for by saturable hepatic uptake. This mechanism, however, is not related to warfarin's metabolic enzymes, which do not show saturation in the dosage range studied.

Animals↗
PubMed1979

Continuing medical education: linking the community hospital and the medical school.

Community hospitals and medical schools have different but complementary resources to carry out continuing medical education. To strengthen the educational capabilities of both, a group of community hospitals has been linked to a medical school in a continuing medical education network. A peripatetic educational development team based at the medical school completes the link by helping community hospital physicians identify educational needs and develop educational responses, using both local and medical school experts as faculty. The educational development team provides skills and staffing which no small or moderate-sized community hospital could afford alone. The program is financially feasible for community hospitals and the medical school, does not consume the resources of either, and conserves the time of the community physician and medical school faculty.

California↗