Successful pregnancy after an arterial switch procedure for complete transposition of the great arteries.
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Adult↗
Biomedical subjects
A van Dijk
Publications and source records attributed to A van Dijk.
Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin.
Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 microg/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients.
Adult↗
Once-daily versus multiple-daily gentamicin in infants and children.
In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels. Fifty-two infants and children aged 1 month (postterm) to 16 years were enrolled. The duration of fever from the start of therapy, the percentage decline of C-reactive protein (CRP) on day 3 of treatment, and the clinical outcome were used as efficacy parameters. Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics in both groups were comparable. A good clinical response was observed in both groups. Fever may have resolved faster with multiple-daily administration, but this was not statistically significant. The percentage of decline of CRP was also comparable in both groups. Nephrotoxicity occurred in six patients, three per group. Many patients were too ill or too young to perform hearing tests, but no clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration) were necessary to meet the target gentamicin levels. Triple-daily doses had to be reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval adaptations can be performed by Bayesian forecasting using a one-compartment model with one set of K(e) and V(d) parameters. The authors consider both regimens equally effective, with a comparable incidence of nephrotoxicity. A starting dose of 6.5 mg/kg once daily is advised.
Adolescent↗
[Meeting concerning the veterinary medicine of the pig by Cehave-Landbouwbelang. Newest insights in nutrition and health].
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Animal Feed↗
[Ethanol for treatment of delirium in alcohol dependent patients on intensive care units in the Netherlands: efficacy not proven].
OBJECTIVE: To determine the use of ethanol in Dutch intensive care departments (ICUs) for the treatment of deliriant symptoms in alcohol-dependent patients, and to study the literature data concerning this use. DESIGN: Literature search and questionnaire. METHOD: In Medline a search was performed from 1993 onward with keywords 'intensive care' and 'alcohol'/'alcohol withdrawal syndrome'/'delirium'. All Dutch ICUs received a written questionnaire (n = 247) concerning the use of ethanol in this patient group. RESULTS: According to the literature the syndrome is characterized by autonomous hyperactivity, resulting in tachycardia, tachypnoea, hypertension, perspiration, fever, tremors en fear. In delirium caused by alcohol withdrawal benzodiazepines are advised, sometimes in combination with haloperidol. ICUs sometimes use ethanol, although the effectiveness in preventing or treating withdrawal symptoms has never been ascertained in scientific investigations: in a meta-analysis the conclusion is drawn that the studies are too small and insufficiently objective to determine the effectiveness. The response to the questionnaire was 55% (96/176). From all ICUs, 15 (16%) used ethanol occasionally, and treated an estimated 17% of the admitted alcohol-dependent patients. There was a tendency for large ICUs to use ethanol in these patients more frequently. Each ICU used its own method to calculate the required ethanol dosage. Calculation on the basis of these dosages indicated a plasma ethanol concentration of at most 0.5 promille. CONCLUSION: Because only a small percentage of deliriums on ICUs are caused by alcohol withdrawal, and the effectiveness of ethanol in alcohol-dependent patients with a delirium has never been proven, the use of ethanol in such cases is discouraged.
Alcohol Withdrawal Delirium↗
Interferon-alpha induced changes in CEA expression in patients with CEA-producing tumours.
Enhancement of antigen expression could result in improved tumour targeting using antibodies directed to the antigen. In this study we performed radioimmunoscintigraphy using 99mTc-CEA-Scan to analyse the effect of interferon-alpha (IFN-alpha) in enhancing the expression of carcinoembryonic antigen (CEA) in ten patients with CEA-producing tumours. Furthermore, we investigated the feasibility of a future therapeutic study with this antibody fragment labelled with rhenium-186. Although IFN-alpha gave rise to a significant increase in antibody uptake by the tumour, the absolute antibody uptake in the tumour appeared to be poor, with a mean of 0.475% of injected dose (ID) in the tumour before IFN-alpha, rising to 0.562% ID in the tumour after IFN-alpha. Pharmacokinetic analysis demonstrated no significant alterations after IFN-alpha. In conclusion, the administration of IFN-alpha is an attractive way to achieve enhanced tumour targeting, although the increase was of little clinical significance in this patient population and using this antibody fragment.
Adult↗
Hemoperfusion is ineffectual in severe chloroquine poisoning.
OBJECTIVES: To study the toxicokinetics in severe chloroquine poisoning, and to evaluate the efficacy of hemoperfusion. DESIGN: Case report on one observation. SETTING: Medical intensive care unit (ICU) of the University Medical Center Utrecht, The Netherlands. PATIENT HISTORY: A previously healthy, 52-yr-old woman ingested 100 tablets containing 100 mg chloroquine base 1 hr before admission. At admission, she was drowsy, agitated, hypotensive, and in respiratory distress. Shortly thereafter, she was resuscitated from cardiac arrest. After hemodynamic and respiratory stabilization, the patient was transferred to the medical ICU. TOXICOKINETICS EVALUATION: During the course of her stay at the ICU, blood samples were taken for the determination of chloroquine and the metabolite desethylchloroquine concentration. Hemoperfusion was started 3.5 hrs after ingestion of the chloroquine tablets. MEASUREMENTS AND MAIN RESULTS: The following toxicokinetics data during this severe chloroquine poisoning were calculated: apparent volume of the central compartment 181 L, apparent volume of distribution 1137 L, half-life in the distribution phase 6.4 hrs, half-life in the elimination phase 392.8 hrs, and total body clearance 2.01 L/hour. The average extraction ratio during hemoperfusion was 0.07, 0.28, and 0.25, in plasma, erythrocytes and whole blood, respectively. The total amount of chloroquine removed by hemoperfusion was only 480 mg (5.3% of the amount ingested). Simulation of a hemoperfusion session over 5 hrs by using a column with an optimal extraction ratio of 1.0 would have removed 1,816 mg chloroquine, only 18.2% of the amount ingested. This limited contribution of hemoperfusion to the total clearance makes it ineffective. CONCLUSION: Hemoperfusion is not effective in severe chloroquine poisoning, even when started (relatively) early in the course of the intoxication. Toxicokinetic evaluation of a chloroquine poisoning should be based on the evaluation of plasma and whole blood concentrations.
Antimalarials↗
Pharmacokinetics and dosing regimen of meropenem in critically ill patients receiving continuous venovenous hemofiltration.
OBJECTIVE: To study the pharmacokinetics of meropenem in critically ill patients with acute renal failure receiving continuous venovenous hemofiltration (CWHF). DESIGN: Prospective, open-labeled study. SETTING: Medical intensive care unit of the University Medical Center Utrecht. PATIENTS: Five critically ill patients receiving CWHF for acute renal failure treated with meropenem for documented or suspected bacterial infection. INTERVENTION: All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval. MEASUREMENTS AND RESULTS: Mean age and body weight of the patients studied were 46.6 yrs (range, 28-61 yrs) and 85.8 kg (range, 70-100 kg), respectively. The following pharmacokinetic variables for meropenem were obtained: mean peak plasma concentration was 24.5 +/- 7.2 mg/L, mean trough plasma concentration was 3.0 +/- 0.9 mg/L, mean terminal elimination half-life was 6.37 +/- 1.96 hrs, mean total plasma clearance was 4.57 +/- 0.89 L/hr, mean CWHF clearance was 1.03 +/- 0.42 L/hr, mean nonrenal clearance was 3.54 +/- 1.06 L/hr, and mean volume of distribution was 0.37 +/- 0.15 L/kg. CONCLUSION: In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CWHF substantially contributed to the clearance of meropenem (23% of mean total plasma clearance). We recommend meropenem to be dosed at 500 mg intravenously every 12 hrs in patients receiving CWHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.
Acute Kidney Injury↗
Effects of rate of pH fall, time of deboning, aging period, and their interaction on veal quality characteristics.
Three groups of veal carcasses were selected on the basis of their pH in the longissimus lumborum muscle at 3 h postmortem (pH3) to study the effects and interaction with time of deboning on quality characteristics of veal. The following groups of 10 calves each were selected: 1) fast pH fall, pH3 < 6.2; 2) intermediate pH fall, 6.2 < pH3 < 6.7; and 3) slow pH fall, pH3 > 6.7. Longissimus thoracis et lumborum (LTL) muscles of sides of the selected carcasses were randomly assigned to be excised at either 24 or 48 h postmortem. Color, water-holding capacity, and shear force measurements were determined after an aging period of 2, 3, 4, 7, and 14 d, respectively. Color of longissimus muscle samples from veal calves with similar preslaughter blood hemoglobin values becomes significantly lighter with a faster pH fall. Muscle color was not affected by time of deboning and overall color of all longissimus samples remained stable during storage and was not affected by rate of pH fall and time of deboning. Cooking losses increased with both a faster rate of pH fall and by deboning at 24 h postmortem. Drip losses during vacuum storage were higher for muscles excised at 24 rather than 48 h postmortem. Both when deboned at 24 and 48 h, postmortem veal carcasses with a lower rate of pH fall had higher shear force (SF) values than did carcasses with a higher rate of pH fall. Deboning at 24 h postmortem resulted in higher SF values than deboning at 48 h postmortem. Differences in SF between 24- and 48-h deboning were larger in slower glycolyzing carcasses. Aging improved tenderness but did not fully reduce the difference in SF values between 24- and 48-h deboning. The results suggest that deboning of veal carcasses before the ultimate pH has been reached may result in muscle contraction, which may exert negative effects on tenderness and water-holding capacity of veal. Effects of time of deboning can, at least partly, be explained by differential effects on shortening of the muscle fibers.
Animals↗
Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients.
OBJECTIVE: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF). DESIGN: Open-label study. SETTING: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht. MATERIALS AND METHODS: In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation. INTERVENTIONS++: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter. MEASUREMENTS AND RESULTS: The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t(1/2 term)) 15.4 h, total clearance (Cl(tot)) 2.5 l/h, CVVHF clearance (CL(CVVHF, form 1)) 1.4 l/h, and body clearance (Cl(body)) 1.1 l/h. The average sieving coefficient during the study period was 0.89 +/- 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, (1/2 term) 20.3 h, Cl(tot) 1.4 l/h, Cl(CVVHF, form 1) 1.4 l/h, and Cl(body) < 0.1 l/h. The average sieving coefficient during the study period was 0.88 +/- 0. 03. The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2. CONCLUSIONS++: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients. The amount of vancomycin removed with CVVHF was about 250 mg per 12 h. A clear difference in body clearance in the two patients was observed. Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15-20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.
Acrylic Resins↗
Can bone marrow scintigraphy predict platelet toxicity after treatment with 186Re-HEDP?
The toxicity of 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) therapy in patients with painful bone metastases is mainly limited to thrombocytopaenia. The aim of this study was to investigate the influence of bone marrow scintigraphy on the prediction of decreased platelet counts after 186Re-HEDP therapy. Twenty-nine prostatic cancer patients with multiple painful bone metastases were included in the study. From a pre-therapy nanocolloid bone marrow scintigram, the bone marrow index (BMI) was determined as an indicator of the extent of bone marrow involvement. The influence of the BMI on the prediction of percent decrease in platelet counts was investigated. The mean BMI was 59 +/- 20. Regression analysis showed that the BMI does not improve the relationship between percent reduction in platelet count and administered dose. In contrast, we previously showed that the bone scan index (BSI) does predict the percent reduction in platelet counts before treatment. We conclude that bone marrow scintigraphy does not provide any additional information on platelet toxicity after a therapeutic dose of 186Re-HEDP. Bone scintigraphy is preferred in the prediction of reduced platelet counts.
Aged↗
Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen.
Population pharmacokinetic parameters of gentamicin in preterm neonates on a once-daily dosage regimen of 3.0 mg/kg given intravenously every 24 hours were established prospectively. In 34 preterm neonates with a mean gestational age of 32 +/- 4 (SD), 182 serum gentamicin levels (91 peak/trough pairs) were determined. Individual adjustments of dose or dosage interval were calculated by computer-aided Bayesian forecasting. The parameters Vd, ke, and CL for each patient were obtained by the nonparametric estimation of maximization method. The predictive power of the model was calculated and the pharmacokinetic estimates were statistically analyzed with SPSS/PC. Cluster analysis showed a division into 2 subpopulations (designated 1 and 2) on the basis of postnatal age. The mean +/- SD postnatal age of subpopulation 1 (n = 29) was 6 +/- 2 days (range 1-7) and of subpopulation 2 (n = 5) 15 +/- 4 days (range 12-24). The mean +/- SD gentamicin relative clearances of subpopulation 1 and subpopulation 2 were 0.0515 +/- 0.0128 and 0.1026 +/- 0.0102 L kg(-1) hr(-1), respectively (p < 0.05). The mean +/- SD values for Vd (Lkg(-1)) in both populations 1 and 2 were 0.6916 +/- 0.1670 and 0.7509 +/- 0.1961, respectively (not significantly different). For ke these data were 0.0744 +/- 0.0200 and 0.1366 +/- 0.0522 (p < 0.05). Statistics showed that the data for Vd and ke of subpopulation 1 were normally distributed (Vd and ke skewness 1.61 and 1.46; kurtosis 3.09 and 3.10 respectively). The model yielded a bias of -0.11 mg/L and a precision of 0.36 mg/L. It is recommended that gentamicin be started in a dosage of 3.5 mg/kg intravenously once-daily under close monitoring.
Age Factors↗
186Re-etidronate in breast cancer patients with metastatic bone pain.
UNLABELLED: The aim of this study was to evaluate the efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (etidronate) in breast cancer patients with painful bone metastases. METHODS: Thirty patients with advanced breast cancer who had metastatic bone pain were treated with 186Re-etidronate using different dosages in a noncomparative, open-label study. Twenty-four patients were evaluated for efficacy (6 patients had incomplete datasets). Dosages varied from 1295 to 2960 MBq (35 to 80 mCi). Efficacy was evaluated according to the multidimensional pain model using a paper-and-pencil diary. The diary was kept twice daily for 8-10 wk (2 wk before through 6-8 wk after 186Re-etidronate treatment). Response was determined with a strict criteria, in which pain intensity (PI), medication index (MI) and daily activities (DA) were core determinants. Response was defined as: (a) Reduced PI > or = 5% while MI and DA were at least constant; or (b) Reduced PI <25% in combination with improvement of MI or DA > or = 25%, without worsening of either factor. Duration of response should always exceed a minimum of 2 wk. RESULTS: Fifty-eight percent (n = 14) of all patients reported a response. The maximum follow-up period was 8 wk. Duration of response ranged from 2 to 8 wk (mean 4 wk). Patients (14/24) not only experienced considerable pain reduction, but in 12 patients this was also accompanied by noteworthy reduction in MI (> or = 25%). No clear dose-response relationship was found. CONCLUSION: With strict pain assessment criteria, 186Re-etidronate showed a response of 58% in the palliative treatment of metastatic bone pain originating from breast cancer.
Bone Neoplasms↗
[Gentamicin dosing regimen for neonates: once daily].
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Anti-Bacterial Agents↗
Nonaccidental endosulfan intoxication: a case report with toxicokinetic calculations and tissue concentrations.
CASE REPORT: A case of nonaccidental endosulfan intoxication in a previously healthy 43-year-old male patient is reported. On admission, the patient had few symptoms, but refractory seizures began 1 hour after ingestion. The patient died on the fourth day after admission showing clinical signs of cerebral herniation confirmed at autopsy. Blood, urine, and tissue samples were analyzed for alpha-endosulfan, beta-endosulfan, and endosulfan sulfate by capillary gas chromatography with electron capture detection. Concentration versus time data for endosulfan were fitted using the program MW/Pharm, assuming complete bioavailability although it is recognized that the bioavailability of endosulfan after ingestion may have been low and the calculated clearance was primarily due to redistribution. Hemoperfusion was shown to be ineffective.
Adult↗
Lead toxicokinetics. Development of a biokinetic model to understand and predict the outcome of treatment.
Quite often physicians contact the Dutch Poisons Control Centre for information on patients with increased lead exposure. The most important questions raised by physicians dealing with these patients are how to estimate the lead exposure and the total lead body burden, how to interpret blood lead concentrations and whether the patient needs treatment. In order to answer these questions we need knowledge of the toxicokinetics of lead in the human body. To achieve insight and to make this knowledge accessible to physicians a biokinetic model for lead metabolism in the human body was developed. A four-compartment model with first-order kinetics, based on the concept of Kneip, was used. A biokinetic model uses a mathematical approach to translate the complex biological and kinetic behaviour of lead. In order to develop this biokinetic model two computer programmes were used. At the moment the model is tested with clinical data from patient treated at the medical toxicology outpatient clinic of the Utrecht University Hospital (this department cooperates very closely with the National Poisons Control Centre). Especially with regard to chelation therapy for elevated blood lead levels due to chronic exposure, the model is very helpful in visualising the toxicokinetics of lead in the human body. Toxicokinetic model might help improve knowledge of lead toxicokinetics, leading to well-considered guidelines for treatment of lead intoxications.
Absorption↗
Iodine-131 therapy in sporadic nontoxic goiter.
UNLABELLED: The effect of radioiodine in the treatment of nontoxic goiter is seldom evaluated quantitatively. The aim of this study was threefold: (a) to assess the effect of 131I on goiter volume, (b) to establish a relationship between CT volume reduction and the amount of radioactivity taken up by the thyroid and (b) to assess the precision of scintigraphic thyroid volume measurements. METHODS: In 27 patients with sporadic nontoxic goiter, the thyroid volume was estimated from a [99mTc]pertechnetate scintigram. Two different models (cylinder model and surface model) were applied. The 131I dosage varied between 507 and 3700 MBq. In all patients, noncontrast CT scanning of the neck was performed before therapy and 1 yr after therapy. RESULTS: The mean CT thyroid volume before therapy was 194 +/- 138 ml. A reduction was obtained in all patients and averaged 34% +/- 17%. The volume reduction measured by CT correlated well with the amount of 131I in the thyroid (r = 0.70). In thyroids larger than 200 ml, both scintigraphic volume estimation methods were imprecise. For smaller volumes, the surface model was superior. Hypothyroidism developed in 14% of the patients. No other side effects occurred. CONCLUSION: Iodine-131 therapy for volume reduction in nontoxic goiter is a safe and effective treatment. For scintigraphic estimation of thyroid gland volumes smaller than 200 ml, the surface model is preferred.
Adult↗
Absorption, kinetics, antibody-bound and free serum determination of a 14C-labeled Escherichia coli extract after single oral administration in rats.
The bioavailability of the major fraction of a 14C-labeled Escherichia coli extract (OM-89) of high molecular mass > 30 kD (HEC) was investigated in rats after a single oral administration of a dose of 100 mg/kg b.w. The determination of radioactivity in blood and plasma showed that HEC was absorbed by the digestive tract, either in its original form or partly degraded. In plasma, the radioactivity reached a Cmax value after 4 h, equivalent to an extract concentration of 31.7 micrograms/g of plasma with an elimination half live of 33 h. High molecular weight molecules of HEC (> 30 kD) were found by radiochromatography in rat serum 4 h after administration. Immunoprecipitation in the serum showed that HEC retains intact determinants throughout the digestive and absorptive processes. It is therefore absorbed either in its original form or partly degraded. A high incorporation of radiolabel was found in liver, secretory glands (adrenals, thyroid gland, pancreas), and in lymphoid organs (spleen, mesenteric lymph nodes).
Adjuvants, Immunologic↗