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Biomedical subjects

J W Mulder

Publications and source records attributed to J W Mulder.

At least 19 recordsLinked to original sources
PubMed2005

Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.

AIMS: To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified. METHODS: The pharmacokinetics of lopinavir in combination with ritonavir were described using NONMEM (version V, level 1.1). First, ritonavir data were fitted to a previously developed model to obtain individual Bayesian estimates of pharmacokinetic parameters. Hereafter, an integrated model for the description of the pharmacokinetics of lopinavir with ritonavir was designed. RESULTS: From 122 outpatients 748 lopinavir and 748 ritonavir plasma concentrations were available for analysis. The interaction between the drugs was described by a time-independent inverse relationship between the exposure to ritonavir over a dosing-interval and the apparent clearance (CL/F) of lopinavir. The model parameters volume of distribution and absorption rate constant were 61.6 l (95% prediction interval (PI) 22.4, 83.7) and 0.564 h(-1) (95% PI 0.208, 0.947), respectively. The model yielded a theoretical value for the CL/F of lopinavir without ritonavir of 14.8 l h(-1) (95%PI 12.1, 20.1), which translates to a value of 5.73 l h(-1) in the presence of ritonavir. The only factor with significant effect on the pharmacokinetics was concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTI), which increased the CL/F of lopinavir by 39% (P < 0.001). CONCLUSIONS: We have developed a model that has defined a time-independent inverse relationship between the exposure to ritonavir and the CL/F of lopinavir, and provided an adequate description of the pharmacokinetic parameters for the latter. Concomitant use of the NNRTIs efavirenz and nevirapine increased the CL/F of lopinavir.

Adult↗
PubMed2005

SHARON process evaluated for improved wastewater treatment plant nitrogen effluent quality.

New stricter nitrogen effluent standards and increasing influent loads require existing wastewater treatment plans (WWTPs) to extend or optimize. At WWTPs with limited aeration capacity, limited denitrification capacity or shortage of aerobic sludge age, implementation of SHARON to improve nitrogen effluent quality can be a solution. SHARON is a compact, sustainable and cost-effective biological process for treatment of nitrogen-rich rejection waters. At WWTP Rotterdam-Dokhaven and WWTP Utrecht a SHARON has been in operation for several years. For both WWTPs the effect of SHARON on the nitrogen effluent quality has been evaluated. WWTP Rotterdam-Dokhaven has limited aeration capacity. By implementation of SHARON, the ammonia load of the effluent was reduced by 50%. WWTP Utrecht had limited denitrification capacity. The implementation of SHARON improved the effluent nitrate load by 40%. The overall TN removal efficiency increased from 65% to over 75% and strict nitrogen effluents standards (TN = 10 mg N/l) could be reached. Through modelling and supported by full scale practice it has been shown that by implementation of SHARON in combination with enhanced influent pre-treatment, the aerobic sludge age can be extended to maintain total nitrogen removal at lower temperatures.

Aerobiosis↗
PubMed2004

Evaluation of clinical pharmacist interventions on drug interactions in outpatient pharmaceutical HIV-care.

OBJECTIVE: To evaluate the usefulness of intervention in drug interactions of antiretroviral drugs with coadministered agents by a clinical pharmacist in outpatient HIV-treatment. METHODS: The study design included two intervention arms (A and B), which were both preceded by a control observation period. In arm A, a complete list of the currently used drugs, extracted from pharmacy records was provided to the treating physician. In arm B the same list was provided but with a notification when a drug interaction was present and an advice how to handle this. The infectious disease specialist obtained the information before the patient's visit to the outpatient clinic (time point 0). Three months prior (time point -3) and 3 months after (time point +3) the intervention, pharmacy records were also screened for drug interactions. The number of drug interactions (total and per patient) was determined at the three different time points (-3, 0, +3). In addition, drug interactions encountered at time points -3 and 0 were checked for their presence at time points 0 and +3, respectively, for both intervention arms. RESULTS: Arms A and B included 115 and 105 patients, respectively. Patient characteristics of both intervention arms were similar at time point 0. The number of interactions and the number of patients with interactions were similar in both intervention arms at time point 0. There were 42 and 40 potential drug interactions in 30 and 24 patients in arms A and B, respectively. The reduction in the number of interactions per patient over time and after intervention was small but significant, and was equal in both intervention arms. The advice of the clinical pharmacist had thus no additional value. CONCLUSION: Both interventions were effective in reducing the number of drug interactions per patient. The advice of a clinical pharmacist was, however, redundant in the studied setting.

Adult↗
PubMed2004

Differential CD4 T-cell response in HIV-1-infected patients using protease inhibitor-based or nevirapine-based highly active antiretroviral therapy.

OBJECTIVES: To study the dynamics of CD4 T-lymphocyte counts (CD4 counts) after the initiation of either protease inhibitor (PI)-based or nevirapine (NVP)-based first-line highly active antiretroviral therapy (HAART). DESIGN AND METHODS: A retrospective cohort study of 1029 HIV-infected antiretroviral therapy-naive patients initiating either PI-based or NVP-based HAART was carried out. Patients were censored as soon as they experienced virological failure, or changed their original antiretroviral regimen for any reason. RESULTS: In total, 920 and 109 patients initiated PI- and NVP-based HAART, respectively. The patients in the PI group more often had AIDS (15 vs. 6% in the NVP group), had a lower median baseline CD4 count (234 vs. 250 cells/microL in the NVP group) and had higher median baseline plasma HIV-1 RNA levels (pVL) (5.0 vs. 4.7 log10 HIV-1 RNA copies/mL in the NVP group). After 96 weeks of follow-up, the mean increase from baseline in CD4 count, adjusted for baseline CD4 count, age, gender and baseline pVL, was 310 cells/microL in the PI group and 212 cells/microL in the NVP group (P=0.003). This difference was mainly attributable to the patients in the NVP group initiating HAART with a baseline CD4 count below 200 cells/microL. There were no differences between the PI and NVP groups with respect to the change in the number of CD4 cells as a proportion of the total number of lymphocytes. CONCLUSION: Patients successfully treated with NVP-based HAART have a smaller increase in absolute CD4 cells compared with those treated with PI-based HAART.

Adult↗
PubMed2002

[Aplasia cutis congenita in 4 infants].

In 4 infants, 3 boys and 1 girl, the congenital absence of skull skin was diagnosed: aplasia cutis congenita, a rare congenital skin defect, which usually presents as a solitary defect over the vertex of the skull measuring a few to approximately 10 centimetres. All four patients were treated with a skin transplantation and more than a year later the skin covered the skull well. There is no consensus concerning the treatment of aplasia cutis congenita. Due to unfamiliarity with this condition, a conservative approach is often adopted. The management strategy indicated should depend on the size of the defect and the child's physical condition. In the case of large defects, an early operative treatment is desirable to prevent serious complications such as haemorrhages and infections. Sufficient skin coverage can be obtained by using rotation scalp flaps, and if necessary additional split-skin grafts. In some patients large rotation flaps are not reliable due to the abnormal vascularity of the skin (Adams-Oliver syndrome). Split-skin grafting is the treatment of choice in these patients.

Female↗
PubMed2002

[Post-exposure treatment against HIV outside of the hospital in Amsterdam, January-December 2000].

The Infectious Diseases Department of the Amsterdam Public Health Service regularly sees people who have possibly been exposed to human body fluids infected with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV), as a result of incidents in either a non-hospital-related occupation or during their leisure time. Until January 2000, people reporting possible exposure were referred to hospitals for HIV post-exposure prophylaxis (HIV-PEP), whereas for HBV and HCV, the tracing of the infection source and the follow-up took place at the Public Health Service clinic. Since the introduction of a new protocol in January 2000, the Public Health Service as well as a hospital can establish an indication for HIV-PEP and prescribe it. In 2000, 322 persons reported to the Public Health Service. The source was tested in 194 incidents and an HIV test was carried out on 104 occasions. In 19 cases HIV antibodies were found or the source was known to be HIV positive. A total of 50 people were prescribed HIV-PEP; 16 times after a needle-stick accident, 22 times after a sexual accident, 6 times after a bite-wound and 6 times after direct exposure to human blood. The sources of 30 PEP recipients could be tested and after this 16 recipients could stop with the treatment due to a negative HIV test. In 4 cases PEP treatment was stopped following a review of the indication. Therefore, 30 people had an indication to complete the PEP treatment. Of these, more than 80% reported side effects and 3 people had to withdraw from the treatment at an early stage because of this. The implementation of the protocol has resulted in less confusion because the follow-up now takes place at one location. Compared to other studies, the average time between exposure and treatment is shorter and compliance is good. In the period up to 15 May 2001, no seroconversions had been observed.

Accidents↗
PubMed2002

Prognostic factors for the clinical effectiveness of fluconazole in the treatment of oral candidiasis in HIV-1-infected individuals.

OBJECTIVE: To identify prognostic factors for the clinical effectiveness of fluconazole in HIV-1-infected patients with oropharyngeal candidiasis. DESIGN AND SETTING: The study was designed as a prospective, open label, non-comparative, dose escalating, single centre trial. PATIENTS AND METHODS: Thirty-four HIV-1-infected patients with oropharyngeal Candida infection were treated with 50 or 100mg fluconazoleday(-1), depending on the clinical manifestation (erythematous or pseudomembranous). The dose was doubled weekly until clinical cure. The predictive value of potential prognostic factors for the duration of treatment and cumulative fluconazole dose until cure was studied: exposure to fluconazole, previous use of fluconazole, the use of antiretroviral drugs, the CD4(+) cell count, erythematous or pseudomembranous appearance, the minimum inhibitory concentration (MIC) for fluconazole of the isolated Candida strain, and xerostomia. RESULTS: Twenty-eight patients (with 30 episodes of oropharyngeal candidiasis) were evaluated. Twenty-five episodes were cured within 1-week of treatment, the remaining five episodes were cured within 2 weeks. No predictive value for any of the studied factors on the duration of fluconazole treatment or the cumulative fluconazole dose until cure was demonstrated. CONCLUSION: Because of the high susceptibility to fluconazole and the positive clinical outcome, the variation in outcome measurements was too modest to establish a significant relationship between any of the investigated potentially prognostic factors and the cumulative fluconazole dose and the duration of treatment to reach cure. On the other hand it can be concluded, that fluconazole is very effective in patients with advanced HIV infection and low CD4(+) cell counts, even if they are not using antiretroviral agents.

AIDS-Related Opportunistic Infections↗
PubMed2002

Detection of late pp67-mRNA by NASBA in peripheral blood for the diagnosis of human cytomegalovirus disease in AIDS patients.

OBJECTIVE: To evaluate the value of late-pp67-mRNA nucleic acid sequence-based amplification (NASBA) in comparison to DNA-PCR, blood culture and pp65-antigenemia assay for the detection of human cytomegalovirus (HCMV) disease in HIV-infected patients. METHODS: The results of pp67-mRNA NASBA, DNA-PCR, culture and pp65-antigenemia assay were compared in 402 whole blood specimens of 98 HIV-infected patients with a low CD4 lymphocyte count who had not yet received highly active antiretroviral therapy (HAART). Thirty-seven samples were obtained from 30 patients with a diagnosis of HCMV disease and 365 samples from 68 patients without HCMV disease. RESULTS: The highest agreement of test results was observed between pp67-mRNA NASBA and quantitative pp65-antigenemia, with a threshold of nine antigen-positive cells/10(5) leukocytes (kappa-value 0.70, 95% CI=0.58-0.82). The sensitivity of pp67-mRNA NASBA for the diagnosis of HCMV disease (59.3%) was identical to that of the quantitative pp65-antigenemia assay, higher than that of the blood culture (48.2%) but lower than that of the DNA-PCR (77.8%). Pp67-mRNA NASBA (92.3%), quantitative pp65-antigenemia assay (92.3%) and blood culture (93.9%) were highly specific for the diagnosis of HCMV disease and as a result, had a higher positive predictive value (76.2, 76.2 and 76.5%, respectively) than the qualitative DNA-PCR (58.3%) and the qualitative pp65-antigenemia assay (47.6%). CONCLUSION: pp67-mRNA NASBA, an easy and rapid to perform assay, well-standardised by virtue of co-amplified internal system control RNA, provides a high specificity and positive predictive value for the diagnosis of HCMV disease in HIV-infected patients, comparable to that of the quantitative pp65-antigenemia assay and blood culture.

AIDS-Related Opportunistic Infections↗
PubMed2001

[HIV-1 therapy in the Netherlands; virological and immunological response to antiretroviral therapy].

OBJECTIVE: To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of since 1996 in the Netherlands available protease and reverse transcriptase inhibitors. DESIGN: Prospective cohort study. METHODS: In an observational clinical cohort of HIV-1-infected individuals, the short-term successful treatment end point of antiviral therapy including at least one antiretroviral drug licensed in the Netherlands since July 1, 1996 (protease inhibitors and reverse transcriptase inhibitors), was HIV-1 RNA plasma levels < or = 500 copies/ml (virological success). Cox proportional hazard models were used to identify prognostic markers for therapy success. The study included 2,148 infected individuals with a median follow-up of 135 weeks of treatment; 1,049 had been pre-treated with antiretroviral drugs before starting their new regimen and 1,099 were treatment naive. RESULTS: Plasma HIV-1 RNA levels < or = 500 copies/ml at 24 weeks of treatment were seen in 61% of all patients. The chance of therapy success for naive patients was twice that for pre-treated patients (relative risk: 1.8; p < or = 0.001). Following the first 24 weeks, the chance of virological success was higher in the naive group (78% versus 63%; p < or = 0.001), and the number of naive patients failing therapy after initial success was smaller compared to pre-treated patients (22% versus 45%; p < or = 0.001). In the naive group, the CD4+ T-cell number increased from 239 to 440 (x 10(6) cells/l) in case of success, and decreased from 150 to 320 in case of treatment failure. HIV-1 related morbidity declined from 0.26 to 0.05 and mortality dropped from 0.07 to 0.03 per person-year of follow-up. Regimens were changed at least once in 76% of patients. Toxicity and therapy failure were the main reasons for regimen changes in naive and pre-treated patients, respectively. CONCLUSION: A combination of antiretroviral drugs, including at least one of the drugs licensed since 1996, led to a drop in HIV-1 plasma concentrations. Morbidity and mortality also decreased. The chance of a better immunological and virological response to the new drug regimens was greatest in therapy-naive patients.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals.

OBJECTIVE: To compare the steady state plasma pharmacokinetics of 1000 mg of saquinavir (SQV) in a soft-gel capsule (SGC) formulation in combination with 100 mg of ritonavir (RTV) (capsules) in a twice-daily dosing regimen in HIV-1-infected individuals with historical controls who used 400 mg of SQV in a hard-gel capsule (HGC) formulation in combination with 400 mg of RTV and to investigate the plasma pharmacokinetics of the 1000 mg/100 mg regimen after normal and high-fat breakfasts. DESIGN: Open-label, crossover, steady-state pharmacokinetic study. METHODS: Six HIV-1-infected individuals who used either 1200 mg of SQV (SGC or HGC) three times daily or 400 mg twice daily in combination with 400 mg of RTV twice daily were included. Each patient was switched to 1000 mg of SQV SGC twice daily in combination with 100 mg of RTV twice daily. After 14 days, the patients came to the hospital for assessment of a pharmacokinetic profile during 12 hours. Patients were randomized to receive a high-fat (+/-45 g of fat) or normal (+/-20 g of fat) breakfast. After 7 days, a second pharmacokinetic profile was assessed after ingestion of the drugs with the alternate breakfast. A noncompartmental pharmacokinetic method was used to calculate the area under the plasma concentration versus time curve (AUC0-12h), the maximum plasma concentration (Cmax), the plasma trough concentration (C12h), and the elimination half-life in plasma (t1/2). The obtained pharmacokinetic parameters were compared with those of 12 patients using SQV HGC (400 mg twice daily) in combination with RTV (400 mg twice daily). RESULTS: The median values of the pharmacokinetic parameters for SQV SGC (1000 mg twice daily, normal breakfast) were: AUC0-12h, 18.84 h*mg/L; Cmax, 3.66 mg/L; C12h, 0.40 mg/L; and t1/2, 3.0 hours. The median values of the pharmacokinetic parameters for SQV HGC (400 mg twice daily, normal breakfast) were: AUC0-12h, 6.99 h*mg/L; Cmax, 1.28 mg/L; C12h, 0.23 mg/L; and t1/2, 3.9 hours. The exposure to SQV in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily was significantly higher than the exposure to SQV in a dosing regimen of 400 mg twice daily in combination with 400 mg of RTV twice daily. The pharmacokinetic parameters of SQV SGC in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily were not significantly different after ingestion of a high-fat or normal breakfast (p >.35). CONCLUSIONS: The combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily resulted in a higher exposure to SQV compared with the exposure to SQV obtained when SQV is used in the 400 mg/400 mg twice-daily combination with RTV. In this small number of patients, no significant differences in exposure were seen after ingestion of either a normal or high-fat breakfast. From a pharmacokinetic perspective, the combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily seems to be a good option for further clinical evaluation.

Adult↗
PubMed2001

[Misinterpretation of nerve damage to the hand and forearm due to variations in the motor innervation].

A 21-year-old man served his ulnar nerve at the level of the left elbow. After nerve suturing only a slight loss of strength in two ulnar intrinsic hand muscles was found. Electromyographic examination revealed the crossing of some motor nerve fibres in the forearm from the median nerve to the ulnar nerve, innervating most of the first dorsal interosseous and the abductor digiti minimi muscle. One and a half years later there was still a loss of strength in the other ulnar muscles and a reduced sensitivity of the ulnar area, without a loss of function. Variations in the motor nerve supply of the hand, in particular connections between the median nerve and ulnar nerve in the forearm and hand are common. A complete transection of the ulnar nerve without complete paralysis of the ulnar intrinsic hand muscles can occur. If these variations are not considered, such a transection can be overlooked.

Adult↗
PubMed2001

A retrospective, cohort-based survey of patients using twice-daily indinavir + ritonavir combinations: pharmacokinetics, safety, and efficacy.

OBJECTIVE: To describe the pharmacokinetics, safety, and efficacy of twice-daily indinavir + ritonavir regimens DESIGN: A cohort-based survey of HIV-infected patients who either used indinavir 800 mg + ritonavir 100 mg twice daily or indinavir 400 mg + ritonavir 400 mg twice daily. METHODS: Data were extracted from a database of samples sent to our laboratory for measurement of indinavir + ritonavir plasma concentrations. Patient characteristics, safety, and efficacy measurements were collected by retrospective chart review. RESULTS: 100 Patients using 800-mg indinavir + 100-mg ritonavir twice daily and 32 patients using 400-mg indinavir + 400-mg ritonavir twice daily were eligible. Median peak and trough concentrations of indinavir were 6.8 and 0.77 mg/L in the 800/100 group and 2.6 and 0.45 mg/L in the 400/400 group. The most frequently found side effects were nausea and vomiting, which occurred in 22.1% and 34.9% of the patients in the 800/100 and the 400/400 groups, respectively. Viral load data were analyzed for patients who switched from 800-mg indinavir three times daily to one of the indinavir + ritonavir twice daily regimens. At the time of switch 63% (800/100 group) and 60% (400/400 group) had an undetectable viral load and this increased to 77% and 70%, respectively, during follow-up. Patients who switched to the 400/400 group discontinued treatment more frequently than patients who switched to the 800/100 group (70% vs. 26%, p =.008). CONCLUSIONS: Indinavir + ritonavir regimens show improved pharmacokinetic properties, allowing twice-daily dosing with food. Clinical data suggest that safety and efficacy is at least as good as with indinavir three-times-daily regimens without ritonavir. Prospective, comparative trials are needed to properly assess the role in HIV therapy of these twice-daily indinavir + ritonavir regimens.

Cohort Studies↗
PubMed2001

The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals.

AIMS: To study the effect of fluconazole on the steady-state pharmacokinetics of the protease inhibitors ritonavir and saquinavir in HIV-1-infected patients. METHODS: Five subjects treated with saquinavir and three with ritonavir received the protease inhibitor alone (saquinavir 1200 mg three times daily, ritonavir 600 mg twice daily) on day 1, and the same protease inhibitor in combination with fluconazole (400 mg on day 2 and 200 mg on days 3 to 8). Pharmacokinetic parameters were determined on days 1 and 8. RESULTS: In the saquinavir group, the median increase in the area under the plasma concentration vs time curve was 50% from 1800 microg l(-1) h to 2700 microg l(-1) h (P = 0.04, median increase: 900 microg l(-1) h; 2.5 and 97.5 percentile: 500-1300), and 56% for the peak concentration in plasma (from 550 to 870 microg l(-1), P = 0.04; median increase: 320 microg l(-1) h, 2.5 and 97.5 percentile: 60-450 microg l(-1)). In the ritonavir group, there were no detectable changes in the pharmacokinetic parameters on addition of fluconazole. CONCLUSIONS: Because of the favourable safety profile of saquinavir, dose adjustments are probably not necessary with concomitant use of fluconazole, as is the case for ritonavir.

Administration, Oral↗