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Jacobus Burggraaf

Publications and source records attributed to Jacobus Burggraaf.

23 records · Page 2Linked to original sources
PubMed2002

Development of an optimal furosemide infusion strategy in infants with modeling and simulation.

BACKGROUND: The optimal dosing strategy for continuous intravenous furosemide infusion is unknown in pediatric patients. Eighteen patients less than 1 year old were studied after cardiac surgery during routine clinical care. The current strategy starts with a continuous infusion of 0.1 mg/kg x h, which may be adapted. METHODS: A pharmacokinetic-pharmacodynamic model was developed that linked furosemide dose to furosemide serum concentrations, renal function (creatinine clearance), and urine output. Various regimens were simulated that adapt according to urine production. The modified dosing schedule was prospectively tested in a subsequent population of 18 pediatric patients after cardiac surgery. RESULTS: Data from the follow-up study suggest that urine production is more controlled for the proposed regimen. CONCLUSIONS: Both the modeling and simulation results and the follow-up study indicated that a bolus dose of 1 mg/kg followed 6 hours later with a 1- or 2-mg/kg loading dose and a 0.2-mg/kg x. h intravenous infusion provides a rational starting point for furosemide therapy after cardiac surgery in pediatric patients less than 1 year old. Adjustment of this regimen every 12 hours in steps of 0.1 mg/kg x h on the basis of clinical assessment should lead to adequate control over urinary output.

Drug Administration Schedule↗
PubMed2002

Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women.

Abdominally obese individuals have reduced 24-h plasma GH concentrations. Their normal plasma IGF-I levels may reflect GH hypersensitivity. Alternatively, obesity-associated hyposomatotropism may cause less biological effect in target tissues. We therefore determined whole-body responsiveness to the anabolic effects of GH in abdominally obese (OB) and normal weight (NW) premenopausal women. A 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index, 21.1 +/- 1.9 kg/m(2)) and six OB (body mass index, 35.5 +/- 1.5 kg/m(2)) women in a cross-over design. Endogenous insulin, glucagon and GH secretion was suppressed by infusion of somatostatin. Whole-body protein turnover was measured using a 10-h infusion of [(13)C]-leucine. GH administration induced a similar plasma GH peak in NW and OB women (49.8 +/- 10.4 vs. 45.1 +/- 5.6 mU/liter). GH, compared with placebo infusion, increased nonoxidative leucine disposal, P < 0.0001) and endogenous leucine appearance (R(a), P = 0.0004) but decreased leucine oxidation (P = 0.0051). All changes were similar in both groups. Accordingly, whole-body GH responsiveness, defined as the maximum response of nonoxidative leucine disposal, leucine R(a), and oxidation per unit of GH, was not different in OB and NW women (0.25 +/- 0.18 vs. 0.19 +/- 0.17 micro mol/kg.h, 0.21 +/- 0.23 vs. 0.13 +/- 0.17 micro mol/kg.h, and -0.10 +/- 0.08 vs. -0.08 +/- 0.05 micro mol/kg.h, respectively). These results indicated that whole-body tissue responsiveness to the net anabolic effect of GH is similar in OB and NW women. Hence, we inferred that hyposomatotropism may promote amino acid oxidation and blunt protein turnover in abdominal obesity. However, hyposomatotropism cannot account for all anomalous features of protein metabolism in abdominally obese humans.

Abdomen↗
PubMed2002

Hyposomatotropism blunts lipolysis in abdominally obese women.

Abdominal obesity is associated with reduced 24-h plasma GH concentrations. It is unclear whether hyposomatotropism in abdominally obese humans is compensated by up-regulation of GH receptor sensitivity or causes less biological effect in target tissues. We, therefore, determined the responsiveness of adipose tissue to the lipolytic action of GH in abdominally obese (OB) and normal weight (NW) postmenopausal women. An iv bolus of recombinant human GH or placebo was randomly administered to eight NW [body mass index (BMI): 22.2 +/- 1.6 kg/m(2)] and eight abdominally OB (BMI: 32.1 +/- 2.6 kg/m(2)) women. Lipolysis was measured by infusion of D5-glycerol and modeled as a function of plasma GH concentrations to describe adipose tissue responsiveness. Similar plasma GH concentration peaks ( approximately 20 mU/liter) were achieved by GH injection in both groups. During placebo conditions, the average plasma GH level was significantly lower in OB compared with NW women (0.74 +/- 0.52 vs. 2.08 +/- 1.18 mU/liter, P = 0.023). Adipose tissue responsiveness, expressed as glycerol rate of appearance per kilogram of fat mass per unit plasma GH concentration was not different in both groups (NW: 1.06, OB: 0.68, P > 0.05). These results suggest that hyposomatotropism in abdominally obese individuals is not compensated by increased adipose tissue responsiveness to GH bio-action and, therefore, blunts lipolysis in these individuals.

Abdomen↗
PubMed2002

Absence of interaction of fondaparinux sodium with aspirin and piroxicam in healthy male volunteers.

OBJECTIVE: Patients undergoing major orthopaedic surgery who are being treated with fondaparinux sodium for prevention of venous thromboembolism may be receiving treatment for coronary artery disease or chronic inflammatory disease of the joints or arthritis. Two separate studies assessed any possible interaction between fondaparinux sodium at steady state and aspirin (acetylsalicylic acid) or piroxicam in healthy volunteers. DESIGN: In the first study a single dose of aspirin 975mg was assessed initially, followed by single doses of aspirin or placebo on the fourth day of an 8-day regimen of subcutaneous fondaparinux sodium (10mg once daily). The second study was a three-way crossover, double-blind, randomised study which investigated fondaparinux sodium 10mg + placebo, fondaparinux sodium 10mg + piroxicam 20mg, or placebo + piroxicam 20mg. METHODS: Both studies obtained plasma concentration-time profiles of fondaparinux sodium administered alone and with aspirin or piroxicam. Noncompartmental parameters - peak concentration, trough concentration, time to reach peak concentration, and area under the concentration-time curve - were obtained. Both studies measured the pharmacodynamic parameters bleeding time and activated partial thromboplastin time (aPTT). Safety was monitored. RESULTS AND CONCLUSIONS: Neither aspirin nor piroxicam influenced the pharmacokinetics of fondaparinux sodium at steady state. Two hours after administration, prolongation of bleeding time with aspirin alone or with aspirin plus fondaparinux sodium was significantly greater than with fondaparinux sodium alone (p = 0.003 and p = 0.004, respectively). No significant differences were observed between aspirin alone or aspirin + fondaparinux sodium in effect on bleeding time. A small decrease in collagen-induced platelet aggregation was observed after administration of piroxicam alone or piroxicam + fondaparinux sodium. A small effect on aPTT was observed; it was similar for fondaparinux sodium whether administered alone or in combination with either aspirin or piroxicam. No serious adverse events were reported.

Adult↗