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H G Heijerman

Publications and source records attributed to H G Heijerman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Population pharmacokinetics of ceftazidime in cystic fibrosis patients analyzed by using a nonparametric algorithm and optimal sampling strategy.

Postinfusion data obtained from 17 patients with cystic fibrosis participating in two clinical trials were used to develop population models for ceftazidime pharmacokinetics during continuous infusion. Determinant (D)-optimal sampling strategy (OSS) was used to evaluate the benefits of merging four maximally informative sampling times with population modeling. Full and sparse D-optimal sampling data sets were analyzed with the nonparametric expectation maximization (NPEM) algorithm and compared with the model obtained by the traditional standard two-stage approach. Individual pharmacokinetic parameter estimates were calculated by weighted nonlinear least-squares regression and by maximum a posteriori probability Bayesian estimator. Individual parameter estimates obtained with four D-optimally timed serum samples (OSS4) showed excellent correlation with parameter estimates obtained by using full data sets. The parameters of interest, clearance and volume of distribution, showed excellent agreement (R2 = 0.89 and R2 = 0.86). The ceftazidime population models were described as two-compartment kslope models, relating elimination constants to renal function. The NPEM-OSS4 model was described by the equations kel = 0.06516+ (0.00708.CLCR) and V1 = 0.1773 +/- 0.0406 liter/kg where CLCR is creatinine clearance in milliliters per minute per 1.73 m2, V1 is the volume of distribution of the central compartment, and kel is the elimination rate constant. Predictive performance evaluation for 31 patients with data which were not part of the model data sets showed that the NPEM-ALL model performed best, with significantly better precision than that of the standard two-stage model (P < 0.001). Predictions with the NPEM-OSS4 model were as precise as those with the NPEM-ALL model but slightly biased (-2.2 mg/liter; P < 0.01). D-optimal monitoring strategies coupled with population modeling results in useful and cost-effective population models and will be of advantage in clinical practice, as it allows pharmacokinetic-pharmacodynamic modeling with sparse data, thus describing the relationship between ceftazidime exposure and response in the treatment of acute exacerbations in patients with cystic fibrosis.

Adult↗
PubMed1995

A cystic fibrosis mutation associated with mild lung disease.

BACKGROUND: Cystic fibrosis is the most common lethal autosomal recessive disorder among whites. Among Dutch patients with cystic fibrosis, delta F508 is the most common mutation and A455E the second most common mutation of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7. A455E is associated with preserved pancreatic function and residual secretion of chloride across membranes. We investigated whether it is also associated with less severe pulmonary disease in patients with cystic fibrosis. METHODS: A total of 33 patients with compound heterozygosity for the A455E mutation were matched according to age and sex with patients who were homozygous for the delta F508 mutation. The pairs were analyzed with respect to the following outcome variables: age at diagnosis, pulmonary-function values, and the frequency of pseudomonas colonization, pancreatic sufficiency, and diabetes mellitus. RESULTS: Cystic fibrosis was diagnosed at a later age in the patients with the A455E mutation than in the delta F508 homozygotes (mean age at diagnosis, 15.0 vs. 3.1 years; P < 0.001). Fewer patients with the A455E mutation had pancreatic insufficiency (21.2 percent vs. 93.9 percent, P < 0.001), and none had diabetes mellitus (0 percent vs. 27.3 percent, P = 0.004). Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were significantly higher in the patients with the A455E mutation (mean FEV1, 73.9 percent of the predicted value vs. 54.3 percent of the predicted value; P = 0.002; mean FVC, 88.7 percent of the predicted value vs. 76.3 percent of the predicted value; P = 0.04). Fewer patients with the A455E mutation were colonized with Pseudomonas aeruginosa (33.3 percent vs. 60.6 percent, P = 0.02). CONCLUSIONS: A455E is a common mutation causing cystic fibrosis in the Netherlands. Although several mutations are known to be associated with less severe pancreatic disease, our findings demonstrate a correlation between the A455E mutation and mild pulmonary disease. Because mortality in this disease depends primarily on the progression of pulmonary disease, patients with the A455E mutation have a better prognosis than patients who are homozygous for the delta F508 mutation.

Adolescent↗
PubMed1995

Effect of rhDNase on lung function and quality of life in adult cystic fibrosis patients.

Accumulation of viscous sputum enhances lung damage in patients with cystic fibrosis. High contents of DNA, released by leucocytes, are the major cause of the high viscosity of this sputum. Recombinant human DNase I (rhDNase) decreases viscoelastic properties of sputum in cystic fibrosis and improves lung function. We have investigated the effect of rhDNase over a period of 6 weeks, 2.5 mg once daily, on lung function and quality of life in 12 adult patients with cystic fibrosis. Significant improvements in FEV1, IVC and daily peak flow values were measured. Airway resistance and FVC did not improve significantly. The cause of the improvements found is probably due to recruitment of previously, due to mucus plugging, unventilated lung areas. In addition, the awareness of symptoms related to sputum retention improved, although subjective parameters on general well-being and physical condition remained unchanged.

Adolescent↗
PubMed1995

The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis.

Bronchial hyperresponsiveness is present in 40-60% of adult patients with cystic fibrosis (CF). Drugs which alter airway hyperresponsiveness have not yet been studied in CF. In this randomized placebo-controlled study, we investigated the effects of an inhaled corticosteroid, budesonide, on lung function and bronchial hyperresponsiveness in adult CF patients, with proven bronchial hyperresponsiveness to histamine. Twelve patients were treated with budesonide, 1600 micrograms day-1, and with placebo during two periods of 6 weeks in a randomized, double-blind, cross-over study. Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine, spirometry and clinical symptom scores. After treatment with budesonide, no significant differences in spirometry were seen, however, bronchial hyperresponsiveness to histamine significantly improved as compared to baseline. Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine. Daily symptom scores showed small, but statistically significant, improvements in dyspnoea and cough after budesonide treatment. There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF. Treatment with oral corticosteroids improved the clinical course of selected CF patients, but was associated with unacceptable adverse effects. We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small, but significant, improvement in bronchial hyperresponsiveness to histamine, and symptoms of cough and dyspnoea in adult CF patients. Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF.

Adolescent↗
PubMed1995

Genetic and clinical features of patients with cystic fibrosis diagnosed after the age of 16 years.

BACKGROUND: Cystic fibrosis is usually diagnosed in childhood, but a number of patients are not diagnosed until adulthood. The aim of this study was to investigate whether patients diagnosed at an older age had a different genetic constitution, manifestations of disease, and prognosis from those diagnosed at an early age. METHODS: Clinical data and results of lung function tests and DNA analysis of 143 adult patients with cystic fibrosis were entered into a computerised database. Patients diagnosed before their 16th birthday (early diagnosis, ED) were compared with those diagnosed at 16 years of age or older (late diagnosis, LD). RESULTS: Mean age of diagnosis of the ED group was 4.6 years compared with 27.7 years for the LD group. Mean (SD) percentage predicted pulmonary function was better for the LD group than for the ED group: forced expiratory volume in one second (FEV1) 72.5 (31.1)% and 52.0 (24.8)%, and forced vital capacity (FVC) 89.8 (25.7)% and 71.9 (23.0)%, respectively. Colonisation with Pseudomonas aeruginosa was present in 70% of the ED group and 24% of the LD group. In the ED group 81% had pancreatic insufficiency compared with only 12% of the LD group. None of the LD group was homozygous for delta F508 compared with 58% of the ED group. In the LD group 72% were compound AF508 heterozygotes and 28% had two non-delta F508 mutations. CONCLUSIONS: Among this group of 143 adult patients with cystic fibrosis late diagnosis is caused mainly by delayed expression and mild progression of clinical symptoms. Late diagnosis is associated with milder pulmonary disease, less pancreatic insufficiency, and different cystic fibrosis mutations. Since mortality in cystic fibrosis depends on the progression of pulmonary disease, patients with a late diagnosis have a better prognosis than those diagnosed early.

Adolescent↗
PubMed1995

Erroneous diagnosis of distal intestinal obstruction syndrome in cystic fibrosis: clinical impact of abdominal ultrasonography.

OBJECTIVE: To describe the use of abdominal ultrasonography in the differential diagnosis of distal intestinal obstruction syndrome (DIOS). DESIGN: Four case reports. SETTING: Adult cystic fibrosis centre (140 patients). PATIENTS: Four cystic fibrosis patients presenting over 18 months with clinical symptoms suggestive of a DIOS which could not be substantiated. OUTCOME: In all cases abdominal ultrasound was valuable in making a diagnosis. CONCLUSION: Abdominal ultrasound is a useful diagnostic tool for differentiating a DIOS from other abdominal conditions.

Adolescent↗
PubMed1995

Inhalation of antibiotics in cystic fibrosis.

Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibiotics in cystic fibrosis were collected by computerized literature search and analysed. Effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles in the respirable range. Twelve studies concerning maintenance treatment were published. Four uncontrolled studies evaluating antibiotic aerosol maintenance treatment in stable patients indicated a beneficial effect in terms of reducing the number of hospital admissions. Eight placebo-controlled studies were found; six of these showed a significant improvement of lung function in the treatment group. Four studies showed a reduction of the number of hospital admissions. In some studies, there was a considerable negative effect of the nebulized placebo solution on the outcome, probably due to the improper choice of its osmolarity. Studies with antibiotic aerosols as adjunct to intravenous therapy in cystic fibrosis patients with an acute exacerbation showed no enhancement of the clinical effects of the intravenous antibiotic by the aerosol; sputum colony counts, however, were lower. Toxicity studies carried out so far have shown no renal or ototoxicity; however, long-term toxicity studies still have to be performed using higher dosages. Introduction or selection of resistant bacteria is relatively rare, but remains a matter of concern. Aerosol maintenance treatment with an appropriate antibiotic in high enough dosage can be recommended for patients with cystic fibrosis chronically infected with P. aeruginosa, and may improve lung function and reduce the number of hospital admissions due to an acute exacerbation.

Administration, Inhalation↗
PubMed1994

Suggestions for the optimization of the initial tobramycin dose in adolescent and adult patients with cystic fibrosis.

Clinical pharmacokinetic data of intravenously administered tobramycin in 34 patients with cystic fibrosis (CF) were correlated with patient parameters. Patients began tobramycin therapy with 10 mg/kg/day in three divided doses. Peak and trough serum concentrations were measured. Tobramycin dose was adjusted to a 30 min postdose peak of 10 mg/L and a predose trough of 1 mg/L. Pharmacokinetic data were calculated according to a one-compartment open model and were correlated with clinical data. Tobramycin half-life and total body clearance did not correlate with age, actual body weight, lean body mass, height, or body surface area. Tobramycin volume of distribution correlated with actual body weight (p < 0.02), lean body mass (p < 0.002), height (p < 0.05), and body surface area (p < 0.01), but not with age. The required daily dose after adjustment to a peak serum concentration of 10 mg/L and a trough level of 1 mg/L correlated with lean body mass (p < 0.02) and body surface area (p < 0.05). Based on our findings, the initial daily dose of tobramycin in patients with CF should be calculated by lean body mass rather than actual body weight or body surface area. A formula is presented to calculate the initial daily dose of tobramycin in CF patients who have normal renal function. Monitoring of tobramycin serum levels remains, however, necessary.

Adolescent↗
PubMed1994

Pharmacokinetics of ceftazidime in adult cystic fibrosis patients during continuous infusion and ambulatory treatment at home.

Acute exacerbations of Pseudomonas aeruginosa lung infections were treated with ceftazidime (CTZ) by continuous infusion (CI) in eight adult cystic fibrosis (CF) patients. CTZ pharmacokinetics were studied after a single dose and during CI (100 mg/kg/24 h) with a CADD-PLUS infusion pump at home for 3 weeks. Individual CTZ pharmacokinetic parameters after single-dose administration were a half-life (t1/2 beta) of 1.90 +/- 0.85 h (mean +/- SD), a volume of distribution (Vs) of 0.28 +/- 0.08 L/kg, and a total body clearance (CL) of 0.152 +/- 0.014 L/h/kg. CL during CI was 0.147 +/- 0.019 L/h/kg, equal to the CL after a single dose. CTZ clearance at the start and at the end of the treatment did not differ. The mean fraction of the dose recovered from the urine was 92.6% (range 85.6-98.5%). Renal clearance was 0.147 +/- 0.015 L/h/kg and was not influenced by the pulmonary exacerbation. The early-morning serum concentrations were significantly higher than the afternoon levels (p < 0.02). The mean CTZ serum concentration during CI was 28.7 +/- 5.0 mg/L. Clinical condition and quality of life improved significantly during and after treatment. With the pharmacokinetic population data from the single-dose study, the CTZ steady-state concentrations during CI could be predicted [precision (root mean squared prediction error) 3.1 mg/L; bias (mean prediction error) 0.4 mg/L]. This method may serve as a model in the development of CTZ continuous-infusion dosage regimens in CF home treatment.

Adult↗
PubMed1994

Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in adult cystic fibrosis patients.

BACKGROUND: Malabsorption due to exocrine pancreatic insufficiency is the main gastrointestinal problem in cystic fibrosis. Despite high doses of pancreatic enzyme supplements it is often not possible to normalize fat absorption. We compared a new high lipase pancreatic enzyme preparation (Pancrease-HL; Cilag, Brussels, Belgium), containing enteric coated microspheres with 25,000 U of lipase, 22,500 U of amylase and 1250 U of protease per capsule, with regular Pancrease capsules, containing 5000 U of lipase, 2900 U of amylase and 330 U of protease per capsule. METHODS: In a randomized double-blind crossover study, 13 cystic-fibrosis patients (6 male, 7 female, mean age 27.7 years) received either four capsules of Pancrease t.d.s. or one capsule of Pancrease-HL t.d.s. Patients took 20 mg omeprazole daily to raise intra-duodenal pH and thus optimize release of enzymes from the enteric coated microspheres. RESULTS: With four capsules of Pancrease t.d.s., mean fat excretion was 15.4% and mean nitrogen excretion was 19.9% vs. 15.5% fat and 19.9% nitrogen excretion with one capsule Pancrease-HL t.d.s. Fat and protein energy loss (as a percentage of total daily intake) was 18.3% with Pancrease and 18.2% with Pancrease-HL. The differences were not statistically significant. Pancrease-HL was well tolerated, with no difference in abdominal pain or general well-being scores. The number and average weight of stools passed remained the same. CONCLUSIONS: One capsule of Pancrease-HL appears to be equivalent to four capsules of regular Pancrease. Treatment with less capsules per day with the same efficacy may facilitate patient compliance.

Adult↗
PubMed1993

[Continuous intravenous home treatment of airway infections using ceftazidime administration via portable pump in patients with cystic fibrosis; a multicenter study].

OBJECTIVE: To study the feasibility and applicability of Home intravenous antibiotic treatment (HIVAT) in cystic fibrosis (CF) patients in the Netherlands. DESIGN: Prospective, multicentre study in CF patients with an exacerbation of a Pseudomonas aeruginosa pulmonary infection using a computerised, ambulatory pump for continuous infusion. METHOD: The effects of HIVAT were studied during one year in 24 CF patients (9 male, 15 female; mean age 23.3 years, range 7-52), who received a total of 39 courses of continuous ceftazidime 100 mg/kg/24 hrs i.v. for 3 weeks delivered by a pump. The treatment was preceded by a 2-3 days in-hospital instruction period. The treatment was supervised by the clinic without home visits. Clinical data and quality of life questionnaires were collected at the start and at the end of treatment and one month later. Statistical analysis was performed using Wilcoxon's rank-sum test for paired samples. RESULTS: No major problems were encountered. The patients as well as their physicians preferred home treatment over in-hospital treatment. 35 out of 37 evaluable courses in 23 patients were efficacious. There were statistically significant improvements in clinical condition and quality of life during the treatment. This improvement lasted at least until one month after the end of treatment. The costs of HIVAT were 48-63% less than the same antibiotic treatment in the hospital. CONCLUSION: HIVAT was feasible and could be applied without major problems in the Netherlands. It proved safe, efficacious and cost-effective.

Adolescent↗
PubMed1993

Improvement of fecal fat excretion after addition of omeprazole to pancrease in cystic fibrosis is related to residual exocrine function of the pancreas.

Pancreatic function tests were performed in 11 adult cystic fibrosis (CF) patients with a fecal fat excretion of more than 10% during treatment with pancrease 2 capsules three times a day. These tests included urinary p-aminobenzoic acid (PABA) excretion, fasting serum trypsin and pancreatic polypeptide (PP), and glucose and insulin in fasting and postprandial serum. Subsequently, the patients entered a double-blind placebo-controlled crossover study to assess the effect of gastric acid inhibition by 20 mg omeprazole on fecal fat excretion. Adjunct therapy with omeprazole resulted in a reduction of fecal fat excretion in patients with residual pancreatic function. This improvement showed significant positive correlations with urinary PABA excretion and the increase in serum PP after the meal (P < 0.02 and P < 0.05), but not with the other parameters studied. Therefore, the addition of omeprazole to pancrease is most successful in CF patients with residual pancreatic function, determined by urinary PABA excretion or incremental PP.

Adult↗
PubMed1993

Chronic obstructive lung disease and respiratory muscle function: the role of nutrition and exercise training in cystic fibrosis.

Malnutrition may be an extremely important complicating factor in patients with a variety of chronic lung diseases. The impact of malnutrition on lung disease and respiratory muscle function has been extensively studied in patients with chronic lung disease due to cystic fibrosis (CF). In patients with CF it appears that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition during childhood seems to be associated with impaired growth and repair of the airway walls. Therefore, in children, when growth in body-length may be expected, prevention of malnutrition is associated with better lung function and improved survival. Nutritional intervention in adults, when no further growth may be expected, will only lead to an increase of body fat. However, when combined with a physical training programme it may lead to an improvement in bodyweight, respiratory muscle function, lung function and exercise tolerance. In addition, this approach will lead to an increase in both respiratory and other muscle mass.

Child↗