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Richard P Koopmans

Publications and source records attributed to Richard P Koopmans.

13 recordsLinked to original sources
PubMed2006

Creatine kinase activity is associated with blood pressure.

BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. METHODS AND RESULTS: We analyzed a stratified random sample of the population of Amsterdam, The Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. CONCLUSIONS: Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

Adult↗
PubMed2006

Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing.

OBJECTIVE: Drug dosing during continuous venovenous hemofiltration (CVVH) is based partly upon the CVVH clearance (Cl(CVVH)) of the drug. Cl(CVVH) is the product of the sieving coefficient (SC) and ultrafiltration rate (Q(uf)). Although it has been suggested that the SC can be replaced by the fraction of a drug not bound to protein (F(up)), the F(up) values as reported in the literature may not reflect the protein binding in critically ill patients with renal failure. We compared the observed Cl(CVVH) (SC x Q(uf)) with the estimated Cl(CVVH) (estimated F(UP) x Q(uf)) and determined the effect on the maintenance dose multiplication factor (MDMF). DESIGN AND SETTING: Clinical study in a mixed ICU in a university hospital. PATIENTS: 45 oligoanuric patients on CVVH (2 l/h). INTERVENTIONS: Timed blood and ultrafiltrate samples. MEASUREMENTS AND RESULTS: Amoxicillin, ceftazidime, ciprofloxacin, fluconazole, metronidazole, and vancomycin were easily filtered (mean SC > 0.7) but not flucloxacillin (mean SC 0.3). Predicted and observed Cl(CVVH) corresponded only for fluconazole and metronidazole. The difference between observed and predicted MDMF was small for all drugs, with the exception of ceftazidime (mean 0.25, 95% CI -0.96 to 1.48) and vancomycin (0.05, -1.34 to 1.45). However, this difference was clinically relevant only for vancomycin, because of its narrow therapeutic index. CONCLUSIONS: Dosing based on predicted CVVH removal provides an as reliable estimate than that based on observed CVVH removal except for those antibiotics that have both a narrow therapeutic index and a predominantly renal clearance (e.g., vancomycin).

APACHE↗
PubMed2006

In-hospital cardiac arrest is associated with use of non-antiarrhythmic QTc-prolonging drugs.

AIMS: QTc interval-prolonging drugs have been linked to cardiac arrhythmias, cardiac arrest and sudden death. In this study we aimed to quantify the risk of cardiac arrest associated with the use of non-antiarrhythmic QTc-prolonging drugs in an academic hospital setting. METHODS: We performed a case-control study in which patients, for whom intervention of the advanced life support resuscitation team was requested for cardiac arrest between 1995 and 2003 in the Academic Medical Centre, Amsterdam, were compared with controls regarding current use of non-antiarrhythmic QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusting for potential confounding factors. RESULTS: A statistically significant increased risk of cardiac arrest (OR 2.1, 95% CI 1.2, 3.5) was observed in patients who received QTc-prolonging drugs (42/140). The risk was more pronounced in patients receiving doses > 1 defined daily dose (OR 2.5, 95% CI 1.1, 5.9), patients taking > 1 QTc-prolonging drug simultaneously (OR 4.8, 95% CI 1.6, 14) and patients taking pharmacokinetic interacting drugs concomitantly (OR 4.0, 95% CI 1.2, 13). CONCLUSIONS: Use of non-antiarrhythmic QTc-prolonging drugs in hospitalized patients with several underlying disease is associated with an increased risk of cardiac arrest. The effect is dose related and pharmacokinetic drug-drug interactions increase the risk substantially. Physicians caring for inpatients should be made aware of the fact that these non-antiarrhythmic drugs may be hazardous, so that potential risks can be weighed against treatment benefits and additional cardiac surveillance can be requested, if necessary.

Aged↗
PubMed2006

Ethnic disparities in the incidence, presentation and complications of malignant hypertension.

BACKGROUND: The incidence of malignant hypertension has declined after the introduction of antihypertensive agents. However, previous reports have suggested that malignant hypertension may be relatively common in multi-ethnic populations. The aim of this study was to compare ethnic disparities in the incidence, clinical characteristics and complications of malignant hypertension. METHODS: A retrospective cohort study on malignant hypertension in a multi-ethnic population in Amsterdam, the Netherlands, between August 1993 and August 2005. RESULTS: A total of 122 patients with malignant hypertension were included, mean age 44 years (+/- 12), 66% were men and 47% were black. The incidence rate remained approximately 2.6 (+/- 0.9) per 100,000 per year and was higher among blacks. Black individuals had higher systolic blood pressure (234 +/- 23 versus 225 +/- 22, P = 0.03) and more renal dysfunction compared with white individuals (39% with serum creatinine > 300 micromol/l versus 22%, P = 0.04). Hypertension was previously diagnosed in 58% of all patients, 37% received medication, and 23% stopped their drugs before admission. Health insurance was absent in 25% of black and 2% of white patients (P < 0.01). Secondary causes were identified in 40% of white and 10% of black subjects (P < 0.01). After a mean follow-up of 4.0 +/- 3.2 years 10% had died and 19% needed renal replacement therapy. Renal failure was more frequent in black than in white individuals (hazard ratio 2.8; 95% confidence interval 1.1-7.2), but mainly because of higher serum creatinine levels at presentation. CONCLUSION: The incidence of malignant hypertension and related renal complications is higher in black compared with white individuals. These differences may be explained by ethnic disparities in blood pressure control, drug adherence and insurance status.

Adult↗
PubMed2005

A rapid and validated HPLC method to quantify sphingosine 1-phosphate in human plasma using solid-phase extraction followed by derivatization with fluorescence detection.

We describe the development and validation of analytical methodology for the determination of sphingosine 1-phosphate (S1P) in plasma. It uses solid-phase extraction (SPE) followed by an automated reversed-phase gradient HPLC column-switching system with a pre-column derivatization with o-phthalaldehyde (OPA) and fluorescence detection. The limit of quantification was determined at 100 ng/ml exogenous sphingosine 1-phosphate with a relative standard deviation for precision and accuracy <15%. The within- and between-day relative standard deviation for precision and accuracy were also less than 15%. This validated method should be suitable to quantify plasma concentration of sphingosine 1-phosphate in relatively large numbers of samples.

Calibration↗
PubMed2004

Microangiopathic hemolysis and renal failure in malignant hypertension.

Renal dysfunction is an important cause of morbidity and mortality in patients with malignant hypertension. Microangiopathic hemolysis (MAHA) related to malignant hypertension may cause renal insufficiency by obstruction of interlobular arteries. We hypothesized that the presence of MAHA is an important indicator of renal dysfunction and recovery in malignant hypertension. We retrospectively analyzed 97 patients admitted between April 1994 and April 2004 with malignant hypertension. MAHA was defined as a low platelet count (<150x10(9)/L) with either an elevated lactic dehydrogenase (>220 U/L) or presence of schistocytes. MAHA was present in 26 of 97 patients (27%). Serum creatinine levels at admission were significantly higher in those with than in those without MAHA: median serum creatinine 690 micromol/L (interquartile range [IQR] 394 to 1105) and 120 micromol/L (IQR 82 to 211), respectively (P<0.01). Macroalbuminuria was present in 88% with versus 41% without MAHA (P<0.01). Patients with MAHA were more often black (73%; P<0.01) and had higher systolic blood pressure (mean 242 mm Hg versus 225 mm Hg; P<0.01). Dialysis was needed in 15 patients with MAHA (58%) versus 2 patients (3%) without MAHA. In 6 patients with MAHA, dialysis could be stopped. Cox regression analysis showed that MAHA and systolic blood pressure were the most important indicators of renal improvement during follow-up, with a hazard ratio of 0.24 (95% confidence interval [CI], 0.08 to 0.75; P=0.01) and 1.02 per mm Hg increase in systolic blood pressure (95% CI, 1.01 to 1.05; P=0.01). In conclusion, MAHA is an important indicator of renal insufficiency and recovery in patients with malignant hypertension.

Adult↗
PubMed2004

Impaired cerebral autoregulation in patients with malignant hypertension.

BACKGROUND: In patients with a malignant hypertension, immediate parenteral treatment with blood pressure-lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. METHODS AND RESULTS: In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V(mean) to MAP phase lead and static CA as the MCA V(mean) to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V(mean) to MAP phase lead was lower (30+/-8 degrees versus 58+/-5 degrees , mean+/-SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA V(mean) decrease was 22+/-4%, along with a 27+/-3% reduction in MAP (from 166+/-4 to 121+/-6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82+/-0.15% cm x s(-1) . % mm Hg(-1); r=0.70+/-0.07). CONCLUSIONS: In patients with malignant hypertension, dynamic CA is impaired. An MCA V(mean) plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA V(mean) decreases almost one on one with MAP.

Adrenal Cortex Hormones↗
PubMed2003

CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic patients.

Clozapine is an effective atypical antipsychotic drug applied in the treatment of resistant schizophrenia. The drug is mainly metabolized by cytochrome P-450 (CYP) enzymes especially the isozyme CYP1A2. Remarkably, the effective dosage varies widely among patients, making it necessary to individualize drug therapy with clozapine. The explanation for dosage variation may be differences in drug metabolism, and more specifically of CYP1A2 activity. This study is aimed at determining to what extent variability in clozapine dose can be explained by pharmacokinetic (PK) factors and more specifically by CYP1A2 activity in effectively treated psychiatric patients. In 22 evaluable patients with a schizophrenic disorder chronically using clozapine, the CYP1A2 activity and the clozapine clearance were estimated. For calculation of the pharmacokinetic parameters of clozapine, population PK software based upon Bayesian analysis was used. Caffeine clearance was estimated with the paraxanthine/caffeine ratio and served as estimate of CYP1A2 activity.A significant linear relationship was found between the clozapine dose and clozapine clearance (R: 0.71; P<0.05), whereas no relationship was found between clozapine dosage and clozapine serum trough concentration. Moreover, individual caffeine and clozapine clearances were found to be significantly related (R: 0.62; P<0.05) as were clozapine dose per kg body weight and P/C mol ratio (R: 0.44; P<0.05). We conclude that CYP1A2 activity is an important determinant of the variability of effective clozapine doses in psychiatric patients.

Adult↗
PubMed2003

Two novel methods for the determination of CYP1A2 activity using the paraxanthine/caffeine ratio.

Cytochrome P450 1A2 (CYP1A2) plays an important role in drug metabolism. Provocation with caffeine is used to estimate CYP1A2 activity, but in most tests a long period of caffeine abstinence has to be taken into account. We compared two novel methods with the currently applied test. The pharmacokinetic (PK) parameters of caffeine and paraxanthine were estimated in eight caffeine-taking healthy volunteers by fitting serum concentration-time data to a two-compartment PK model. Then a three-step approach was followed. Step 1: The caffeine administration regimens of three provocation methods, which differ by their periods of abstinence, together with the PK parameters of each volunteer, were entered in a PK simulation program and the molecular ratio of the paraxanthine/caffeine concentration (P/C molratio) of each method was estimated for the individual volunteers. Step 2: For each method a relationship for the population between the caffeine clearance (Clc) and the corresponding P/C molratio was empirically established. Step 3: The true caffeine clearance (Clc tr) of each volunteer, as found by fitting the individual PK curve, was compared for all three methods with the clearance estimated from the individual P/C molratio using the relationship of step 2. The predictive values for Clc of the three methods did not differ significantly from Clc tr. For the three methods the values for bias were 6.7, 4.3 and 3.1%, respectively and for precision they were 12.3, 20.6 and 17.8%. We conclude that the two novel methods of caffeine provocation show good predictive performance for Clc when compared with the conventional method. Abstaining from caffeine for a long period is not necessary to estimate CYP1A2 activity (using the P/C molratio) accurately.

Adult↗
PubMed2003

Pharmacogenetics of hypertension treatment: a structured review.

The extent of blood pressure lowering by anti-hypertensive agents is difficult to predict for individual patients, even when evaluated in the context of biochemical or demographic information. Genetic predictors (mainly single nucleotide polymorphisms, SNPs) have been the focus of several recent studies and are gaining much attention. We have conducted a literature search for studies in which the lowering of ambient blood pressure by specific drugs or drug classes in humans was related to specific genotypes. Twenty-eight studies were identified, of which six had a single-dose design, and the remaining 22 studied drug effects after more than 4 weeks of drug administration. Virtually all were association studies. Prospective trials that compared the prognostic value of genetic methods to routine clinical practice were not identified. Almost all studies used a candidate-gene design, usually with a very small number of SNPs (typically one). Gene-gene and gene-environment interactions were studied only rarely. Only one study targeted genes involved in drug metabolism. Most candidate-genes were part of the renin-angiotensin system. By far the most extensively studied has been the angiotensin-converting enzyme insertion/deletion polymorphism (15 studies) but, to date, no clear picture has emerged for this or other genetic variants. Thus, the potential for utility of genetic characterization of individual patients as a predictor of anti-hypertensive response has yet to be realized.

Angiotensinogen↗