Search PubMed⌕ Search

Biomedical subjects

W Bakker

Publications and source records attributed to W Bakker.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

Validation of tobramycin monitoring in adolescent and adult patients with cystic fibrosis.

The predictive performance of a dosage calculation method for the optimization of tobramycin therapy was studied retrospectively in 29 patients with cystic fibrosis. The dosage calculation method was based on a linear one-compartment open model. It used peak and trough serum concentrations of the aminoglycoside. Bias in the peak concentration was 0.20 mg/L and precision was 1.2 mg/L. Bias in the trough concentration was -0.06 mg/L and precision was 0.33 mg/L. The results were clinically satisfactory. Comparison with previously published results of the predictive performance of other dosage calculation methods showed that the method studied was at least as good.

Adolescent↗

Maintenance chemotherapy in small-cell lung cancer: long-term results of a randomized trial. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: The present study investigates the role of short chemotherapy (five cycles) versus prolonged (12 cycles) chemotherapy in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Six hundred eighty-seven patients with SCLC were registered in a multicenter study to receive five cycles of chemotherapy consisting of cyclophosphamide 1 g/m2 on day 1, doxorubicin 45 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1, 3 and 5 (CDE), every 3 weeks. Four hundred thirty-four nonprogressing patients after five cycles of chemotherapy were randomized either to receive seven further cycles of the same chemotherapy or to follow-up. RESULTS: The response rate of 585 assessable patients was 79%, with 36% attaining a complete response. Toxicity was mainly hematologic, with 16 toxic deaths (2.4% of all eligible patients), 13 of which were due to sepsis. Median survival time from registration of all patients was 326 days (396 and 267 days for limited and extensive disease, respectively) with 3.2% of patients alive at 5 years. No difference in survival between the two arms was observed, with the same number of 5-year survivors in both arms. The patients randomized to the maintenance arm had a progression-free survival (PFS) duration approximately 2 months longer than the patients randomized to follow-up (median of 177 days v 114 days from randomization; P = .0004). Among patients with a partial response who were randomized to receive maintenance chemotherapy, 12 achieved a complete response after 12 cycles. More patients in the follow-up arm than in the maintenance arm received subsequent treatment on progression and responded more frequently to that treatment. Twelve patients developed second malignancies (seven non-small-cell lung cancers). CONCLUSION: Prolonged chemotherapy does not offer a better chance of cure than short chemotherapy (five cycles) and does not prolong survival in patients with SCLC. Short, combination chemotherapy appears to be a reasonable choice for standard treatment of SCLC and for attempts to improve the cure rate of this disease.

Adult↗

Quantitative assessment of pancreatic function by magnetic resonance in cystic fibrosis.

To determine the value of magnetic resonance imaging in the analysis of pancreatic function in cystic fibrosis, 11 adult cystic fibrosis patients with exocrine pancreatic insufficiency were studied by magnetic resonance and a set of non-invasive tests of exocrine and endocrine pancreatic function. Magnetic resonance imaging, comprising the calculation of intensity ratios (pancreas/liver) of the pancreas on T1 ([SE] TR/TE = 300/20) and T2 weighted ([SE] TR/TE = 2000/50-100)images and the measurement of several dimensions of the pancreas, was compared with the results of the indirect pancreatic function tests. Although magnetic resonance showed the typical morphology of the insufficient pancreas in cystic fibrosis, including atrophy, lobular fatty enlargement and infiltration, it was not related to the quantitative exocrine and endocrine function assessed by indirect pancreatic function tests.

Adult↗

Clearance of 99mTc-DTPA and experimentally increased alveolar surfactant content.

We measured clearance of 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of 99mTc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only.

Ambroxol↗

Nutritional state and lung disease in cystic fibrosis.

The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view 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 appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

Cystic Fibrosis↗

Omeprazole enhances the efficacy of pancreatin (pancrease) in cystic fibrosis.

We studied the effect of the addition of omeprazole (20 mg once a day) to treatment with pancreatin (Pancrease, Cilag, Herentals, Belgium), two or four capsules three times a day, on fecal fat excretion in a double-blind, crossover fashion in nine patients with cystic fibrosis having persistent steatorrhea while taking Pancrease, two capsules three times a day (mean fecal fat excretion, 22.3%; range, 12% to 44%). Neither doubling of the dose of Pancrease nor addition of omeprazole to the lower dose of Pancrease significantly reduced fecal fat excretion (mean, 19.6% [range, 10% to 34%]; mean, 16.4% [range, 6% to 32%], respectively). However, addition of omeprazole to the higher dose of Pancrease (four capsules three times a day) significantly reduced fecal fat excretion when compared with the two doses of Pancrease alone (mean, 10.7%; range, 4% to 25%; P less than 0.01). We conclude that adjunct therapy with omeprazole reduces fecal fat excretion in cystic fibrosis provided that a high dose of Pancrease is supplied.

Adult↗