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Biomedical subjects

H J Schouten

Publications and source records attributed to H J Schouten.

At least 19 recordsLinked to original sources
PubMed2005

Genomic cloning and linkage mapping of the Mal d 1 (PR-10) gene family in apple (Malus domestica).

Fresh apples can cause birch pollen-related food allergy in northern and central European populations, primarily because of the presence of Mal d 1, the major apple allergen that is cross-reactive to the homologous and sensitizing allergen Bet v 1 from birch. Apple cultivars differ significantly in their allergenicity. Knowledge of the genetic basis of these differences would direct breeding for hypoallergenic cultivars. The PCR genomic cloning and sequencing were performed on two cultivars, Prima and Fiesta, which resulted in 37 different Mal d 1 gDNA sequences. Based on the mapping of sequence-specific molecular markers, these sequences appeared to represent 18 Mal d 1 genes. Sixteen genes were located in two clusters, one cluster with seven genes on linkage group (LG) 13, and the other cluster with nine genes on the homoeologous LG 16. One gene was mapped on LG 6, and one remained unmapped. According to sequence identity, these 18 genes could be subdivided into four subfamilies. Subfamilies I-III had an intron of different size that was subfamily and gene-specific. Subfamily IV consisted of 11 intronless genes. The deduced amino acid sequence identity varied from 65% to 81% among subfamilies, from 82% to 100% among genes within a subfamily, and from 97.5% to 100% among alleles of one gene. This study provides a better understanding of the genetics of Mal d 1 and the basis for further research on the occurrence of allelic diversity among cultivars in relation to allergenicity and their biological functions.

Allergens↗
PubMed2005

Resistance gene analogues identified through the NBS-profiling method map close to major genes and QTL for disease resistance in apple.

We used a new method called nucleotide-binding site (NBS) profiling to identify and map resistance gene analogues (RGAs) in apple. This method simultaneously allows the amplification and the mapping of genetic markers anchored in the conserved NBS-encoding domain of plant disease resistance genes. Ninety-four individuals belonging to an F1 progeny derived from a cross between the apple cultivars 'Discovery' and 'TN10-8' were studied. Two degenerate primers designed from the highly conserved P-loop motif within the NBS domain were used together with adapter primers. Forty-three markers generated with NBS profiling could be mapped in this progeny. After sequencing, 23 markers were identified as RGAs, based on their homologies with known resistance genes or NBS/leucine-rich-repeat-like genes. Markers were mapped on 10 of the 17 linkage groups of the apple genetic map used. Most of these markers were organized in clusters. Twenty-five markers mapped close to major genes or quantitative trait loci for resistance to scab and mildew previously identified in different apple progenies. Several markers could become efficient tools for marker-assisted selection once converted into breeder-friendly markers. This study demonstrates the efficiency of the NBS-profiling method for generating RGA markers for resistance loci in apple.

Amino Acid Sequence↗
PubMed2001

The effect of glutamate infusion on cardiac performance is independent of changes in metabolism in patients undergoing routine coronary artery bypass surgery.

In a double-blind randomized placebo-controlled study, the effects of intravenous glutamate infusion on myocardial haemodynamics and metabolism were studied in 22 patients undergoing routine coronary artery bypass graft (CABG) surgery. Immediately after aortic cross-clamp release, an intravenous infusion of a solution of glutamate (125 mmol x l(-1)) at a rate of 1.5 ml x h(-1) x kg(-1) was given over 1 h to 11 patients (G group). The other 11 patients received a placebo infusion (0.9% NaCl) (P group). Haemodynamic functions and rates of exchange of glucose, non-esterified fatty acids and lactic acid over the heart were measured before sternotomy (T1), 40 min after cross-clamp release (T2) and 4 h after cross-clamp release (T3). At T2, decreases were seen in comparison with T1 in systemic vascular resistance index, and increases were seen in cardiac index and coronary sinus flow. All of these changes were greater in the G group than in the P group (P<0.05). Myocardial glutamate consumption increased 2-fold after glutamate administration. No significant changes were observed in the myocardial utilization of glucose, lactate or non-esterified fatty acids between the P and the G groups at T1, T2 or T3. These data show that an intravenous glutamate infusion after routine CABG surgery significantly improved cardiac haemodynamic performance without direct effects on cardiac substrate metabolism. This suggests that a reduction of the afterload via a peripheral vasodilatory effect is the main mechanism leading to the observed changes in haemodynamics. Earlier claims that patients with post-operative cardiac failure show metabolic benefits from the glutamate infusion do not seem to apply to patients undergoing routine CABG surgery.

Adult↗
PubMed2000

Combined evidence from multiple outcomes in a clinical trial.

Clinical investigators are encouraged to apply recently developed statistical methodology. For each patient in a trial, favorable and unfavorable results from multiple outcomes may be summarized in a suitable summary measure. This summary measure may be used in a two-sample t-test to decide which treatment is best. An example illustrates how the evidence from the main outcome criteria may be combined. The required study size depends on the mean treatment effect on the outcomes in the summary measure. When separate outcomes are considered, there is a multiple comparisons problem, for which Hochberg offered a simple solution. Evaluation of a single-summary measure may require a larger or a smaller study size than evaluation of separate outcomes, depending on whether treatment effects are about the same or very different.

Clinical Trials as Topic↗
PubMed2000

Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy.

BACKGROUND: Although Kupffer cells (KCs) are capable of producing important growth-stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood. METHODS: In the present study liver regeneration was studied after KC-depletion by intravenous administration of liposome-encapsulated dichloromethylene-diphosphonate (C12MDP), a method known to physically eliminate KCs. Furthermore, splenectomy was performed one week prior to PH to exclude the effect of C12MDP-liposomes on macrophage populations in the spleen. RESULTS: KC-depletion was confirmed in cryostat liver sections stained with the monoclonal antibody ED2, a marker for resident tissue macrophages. Forty-eight hours after PH, the cumulative hepatocyte DNA synthesis, as determined in liver sections by the hepatocyte bromodeoxyuridine labeling index, was significantly decreased in KC-depleted rats when compared to control-rats. The weight of the remnant liver, expressed as a percentage of the initial liver weight, was significantly less at 96 h after PH in KC-depleted rats. KC-depletion abolished the hepatic interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA synthesis and decreased hepatic expression of tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF) and transforming growth factor-beta1(TGF-beta1) mRNA after PH, as was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Moreover, at 4 h after PH the systemic release of IL-6 was significantly decreased in KC-depleted rats. CONCLUSION: We conclude that KCs are important for hepatocyte regeneration after PH. Delayed liver regeneration in KC-depleted rats can be explained, at least in part, by an imbalanced hepatic cytokine expression, thereby suppressing important growth-stimulating cytokines.

Animals↗
PubMed2000

Diagnosing sensory abnormalities with either normal values or values from contralateral skin: comparison of two approaches in complex regional pain syndrome I.

BACKGROUND: To diagnose sensory abnormalities, patient values can be compared with values of the general population (absolute approach) or to values measured at contralateral homologous skin (relative approach). The current study gives normal values for both approaches and compares the advantages of each method by applying the technique to patients with complex regional pain syndrome type I (CRPS I). METHODS: In 50 healthy control subjects, sensory and pain thresholds were measured for pressure, warmth, and cold on both wrists and both feet. In 53 patients with unilateral CRPS I (33 hand, 20 foot), the same assessments were conducted twice, at an interval of 1 month. RESULTS: In control subjects, contralateral homologous sides have approximately the same sensitivity, supporting the validity of the relative approach in patients. Hypoesthesia and allodynia can be diagnosed by either the absolute or relative approach, whereas hyperesthesia and hypoalgesia can only be identified with the relative approach. The two approaches obtain different results in 20% of cases. Age, gender, and subject criteria may influence the absolute but not the relative approach. Both approaches are comparable with regard to reproducibility. Frequency distributions of sensory abnormalities in chronic CRPS I are presented. The most frequent diagnoses were cold allodynia and mechanical hypoesthesia and allodynia. CONCLUSIONS: To divide sensory characteristics into a binary classification of "normal" and "abnormal," the relative approach is the best choice, with the exception of cases in which the contralateral homologous side is absent or affected by disease. The authors recommend the relative approach for both research and clinical purposes.

Adult↗
PubMed1999

Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.

OBJECTIVE: To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice. DESIGN: Randomised controlled trial. PARTICIPANTS: 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years. SETTING: Primary care in the Netherlands. INTERVENTIONS: Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2). MAIN OUTCOME MEASURES: Stroke, systemic embolism, major haemorrhage, and vascular death. RESULTS: 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors. CONCLUSION: In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice.

Aged↗
PubMed1999

Planning group sizes in clinical trials with a continuous outcome and repeated measures.

Simple formulae have been derived for the accurate computation of sample sizes when the two-sample t-test is used. Required sample sizes may be reduced by taking repeated measures, especially if correlations are about equal. In a trial with two parallel groups, repeated measures may be summarized by a pre-treatment mean and a post-treatment mean. In a cross-over trial measures may be repeated within each treatment period. In case the difference between two independent groups increases in time, individual slopes may be used if the correlation between two measures hardly depends on distance in time between these measures. However, it may be more efficient to use only the first and last measure in the statistical test if correlations strongly depend on time distance.

Analysis of Variance↗
PubMed1999

Primary prevention of arterial thromboembolism in nonrheumatic atrial fibrillation: the PATAF trial study design.

Patients with nonrheumatic atrial fibrillation (NRAF) have a higher risk of thromboembolism than patients in sinus rhythm. Several trials have been conducted to establish the best preventive regimen in patients with NRAF, but not in the primary-care setting. The Primary Prevention of Arterial Thromboembolism in Nonrheumatic Atrial Fibrillation (PATAF) study, a primary-care-based trial, was set up to compare the preventive efficacy of low-intensity anticoagulation (AC), target range International Normalized Ratio (INR) 1.1 < INR < 1.6 and regular-intensity AC (2.5 < INR < 3.5) therapies with that of aspirin 150 mg/d for the occurrence of thromboembolism in NRAF patients. Patients eligible for regular-intensity AC were randomly assigned to aspirin at 150 mg/d, low-intensity AC, or regular AC in group I. In cases of noneligibility for regular AC, the trial randomized patients between aspirin and low-intensity AC (assigned to group II). Primary outcome events were stroke (including intracranial hemorrhage), systemic embolism, major hemorrhage, or vascular death. Analysis of the data was based on Cox regression to compute the hazard ratio (HR) with a 95% confidence interval, using the likelihood ratio test. The trial randomized 729 patients. Patient enrollment and follow-up has been stopped, and the final analysis is now complete. We shall publish the main results as soon as possible.

Aged↗
PubMed1999

The effect of paracetamol, fentanyl, and systematic assessments on children's pain after tonsillectomy and adenoidectomy.

Various clinical protocols are used to manage early postoperative tonsillectomy and/or adenoidectomy (T&A) pain in children. Although believed to be effective, these protocols are not evidenced-based. Therefore, a double-blind, randomized, placebo controlled (2 x 2) factorial design was used (1) to evaluate the effectiveness of 2 pain protocols used interchangeably to manage early postoperative T&A pain and (2) to investigate whether nurses' systematic pain assessments improve pain management. In the first protocol children receive a loading dose (30 to 50 mg/kg) of paracetamol (acetaminophen) Formularium der Nederlandse Apothekers (Formulary of the Dutch Royal Society for the Advancement of Pharmacy) intraoperatively, followed by regular doses (70 to 100 mg/kg/24 hours) of paracetamol. In the second protocol children receive the first protocol, plus intramuscular fentanyl citrate (1 microgram/kg) intraoperatively. Subjects were 83 healthy children between the ages of 3 and 12 years, admitted for T&A as an outpatient procedure. The child's pain was measured using observation scales (Children's Hospital of Eastern Ontario Pain Scale and Face Legs Activity Cry Consolability Scale), a visual analogue scale, and self-report measures (Faces Pain Scale and Oucher). Neither pain protocol sufficiently relieved early postoperative T&A pain, and systemic pain assessments did not improve the effectiveness of analgesics. Further research evaluating the effectiveness of pain management protocols is needed.

Acetaminophen↗
PubMed1999

A rational request behavior: the development of prediction instruments regarding thyroid function tests in primary care.

A prospective study was performed to encourage a rational thyroid-stimulating hormone (TSH) test request behavior of physicians, using prediction instruments. The latter give direct feedback about request adequacy on the basis of pretest probabilities of hyperthyroidism using patients' signs and symptoms. For instrument design, stepwise logistic regression was used on diagnostic data acquired through questionnaires, answered by 80 physicians and 668 patients for whom physicians requested a TSH test. Instruments were designed for clinical and subclinical hyperthyroidism and for clinical hyperthyroidism alone. Use of the instrument for clinical or subclinical hyperthyroidism on the selected group, at a 5% probability threshold, can result in a 37% reduction of unnecessary TSH test requests. With the instrument for clinical hyperthyroidism at a 5% probability threshold, the number of unnecessary test requests can be reduced by 57%. Therefore, it can be concluded that the instruments can determine TSH test request adequacy and encourage a rational TSH test request behavior of physicians at low pretest probability thresholds.

Adolescent↗
PubMed1998

No relevant seasonal influences on office and ambulatory blood pressure: data from a study in borderline hypertensive primary care patients.

Our objective was to study seasonal influences on office and ambulatory blood pressure. We therefore designed a prospective 7-month study of 47 borderline hypertensive patients in a primary care setting. We used no interventions. Our main outcome measures were the differences between summer and winter office and ambulatory blood pressures and 95% confidence intervals. Results showed that winter minus summer differences ranged from 0 to 3 mm Hg. Only one significant difference was found: ambulatory systolic daytime pressure was significantly higher (3 mm Hg) in winter than in summer. Our results do not confirm the data of earlier studies in hypertensives. In view of the small and clinically irrelevant winter-summer differences, it seems unnecessary to modify antihypertensive treatment of borderline hypertensives according to the season.

Adult↗
PubMed1998

A series of self-measurements by the patient is a reliable alternative to ambulatory blood pressure measurement.

BACKGROUND: Several studies have reported overdiagnosis and overtreatment of hypertensive patients, especially in borderline hypertensives. AIM: To find a blood pressure measurement procedure that reduces the risk of misclassification to an acceptable level. METHOD: Comparative, prospective study over seven months of primary care patients with elevated initial blood pressures. Blood pressure measurements made by general practitioners (GPs), practice nurses, and patients were compared with ambulatory blood pressure measurements. RESULTS: Ninety-nine patients completed the study. Mean differences (systolic blood pressure) between different measurement procedures and ambulatory measurement ranged from +10 mmHg (doctor) to -1 mmHg (patient), and (diastolic) from +4 mmHg (doctor) to -2 mmHg (patient). Standard deviations of mean differences ranged from 12 mmHg (doctor/systolic) to 10 mmHg (patient/systolic), and from 8 mmHg (doctor/diastolic) to 7 mmHg (patient/diastolic). CONCLUSION: Self-measurements by the patient appear to be a reliable alternative to ambulatory blood pressure measurement. In diagnosing and managing mild hypertension, we recommend the use of a valid self-measuring device.

Adult↗
PubMed1997

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.

Adult↗
PubMed1997

Is a series of blood pressure measurements by the general practitioner or the patient a reliable alternative to ambulatory blood pressure measurement? A study in general practice with reference to short-term and long-term between-visit variability.

We studied the reproducibility of a series of blood pressure measurements by general practitioner (GP) and patient in comparison with that of ambulatory blood pressure measurement (ABPM), with reference to short-term and long-term between-visit variability using a prospective, comparative diagnostic study. The study group was 88 potentially hypertensive primary care patients (initial systolic blood pressure [SBP] between 160 and 200 mm Hg or with diastolic blood pressure [DBP] between 95 and 115 mm Hg). ABPMs were measured on 2 separate days (at a 6 month interval). Two series of measurements by the doctor (at 1 to 6 month intervals), and the patient (at a 1 week interval) were measured. Mean differences and standard deviations of mean differences (SDD) between two successive series of measurements, and between two ABPMs were computed. The Wilcoxon signed-ranks test was used to compare these standard deviations. Mean initial office-blood pressures were 161 (SBP) and 102 (DBP) mm Hg. Long-term between-visit variability (measurements by GP) was larger than short-term between-visit variability: SDDs were 16 v 11 mm Hg (SBP), and 10 v 8 mm Hg (DBP). The differences in average SBP and DBP between successive ABPMs and between successive series of office measurements by GP and home measurements by patient were not statistically significant. Mean differences between two series of measurements by GP and patient, and between two ABPMs, were 0 +/- 1 mm Hg. SDDs between successive ABPMs and series of measurements by GP and patient ranged from 8 to 11 mm Hg (SBP), and were 6 mm Hg (DBP). No statistically significant differences were found between the SDDs of the studied measurement procedures (SBP and DBP). In our study the reproducibility of ambulatory blood pressure measurement was not found to be better than that of a series of four duplicate measurements by GP or patient. Long-term (6 months interval) between-visit variability was larger than the short-term (1 week interval) between-visit variability.

Adult↗