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A Bakker

Publications and source records attributed to A Bakker.

At least 55 records · Page 3Linked to original sources
PubMed1999

An IL-13 promoter polymorphism associated with increased risk of allergic asthma.

IL-13 plays a crucial role in the development of allergic asthma by several mechanisms, including induction of IgE antibodies, airway eosinophilia and hyper-reactivity. We previously established a deregulated production of IL-13 by T cells from allergic asthma patients. In this report we describe the identification of a novel IL-13 promoter polymorphism (C to T exchange) at position -1055. The IL-13 -1055 TT genotype is associated with allergic asthma (P = 0.002), altered regulation of IL-13 production (P < 0.002), and increased binding of nuclear proteins to this region. We postulate that the presence of this polymorphism predisposes to the development of allergic asthma.

Asthma↗
PubMed1999

Excess stroke among hypertensive men and women attributable to undertreatment of hypertension.

BACKGROUND AND PURPOSE: Most population-based studies indicate that a considerable proportion of hypertensive subjects are undertreated and that undertreatment is more prevalent among hypertensive men than among hypertensive women. The aim of our study was to investigate the consequences of undertreatment of hypertension for women and men in terms of stroke occurrence. METHODS: Approximately 45 000 men and women aged >/=20 years were examined in 2 population-based studies in the Netherlands. A cohort of 2616 hypertensive subjects (pharmacologically treated hypertensives and untreated hypertensives who needed pharmacological treatment according to the severity of their hypertension and the coexistence of additional cardiovascular risk factors) was selected for a follow-up study. Follow-up (mean duration, 4.6 years) was complete for 2369 (91%) of the enrolled hypertensive subjects. RESULTS: Compared with treated and controlled hypertensives, the relative risks of stroke for treated and uncontrolled hypertensives and for untreated hypertensives who needed treatment were 1.30 (95% CI, 0.70 to 2.44) and 1.76 (95% CI, 1.05 to 2.94), respectively. These relative risks and the prevalence of (undertreated) hypertension in the total population of 45 000 subjects were used to estimate the number of strokes in the Netherlands attributable to undertreatment. Among hypertensive men and women aged >/=20 years in the Netherlands, the proportions of strokes attributable to treated but uncontrolled blood pressure were 3.1% (95% CI, -5.2% to 18.7%) and 4.1% (95% CI, -7.2% to 20.7%), respectively. For untreated hypertensive men and women who should have been treated, these proportions were 22.8% (95% CI, 0.8% to 38.4%) and 25.4% (95% CI, 0. 5% to 42.5%), respectively. CONCLUSIONS: Increasing the detection of hypertension and improving adherence to current guidelines might prevent a considerable proportion of the incident strokes among hypertensives. The potential impact of achieving control of blood pressure in patients already being treated on the reduction of strokes requires further investigation.

Adult↗
PubMed1999

Paroxetine, clomipramine, and cognitive therapy in the treatment of panic disorder.

BACKGROUND: This 12-week, placebo-controlled study was carried out to compare the relative efficacy of paroxetine, clomipramine, and cognitive therapy in the treatment of DSM-III-R-defined panic disorder with or without agoraphobia. METHOD: After a 3-week single-blind, placebo run-in period, 131 patients were randomly assigned to receive double-blind medication or 12 sessions of cognitive therapy based on the model of Clark. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression scale, the Patient Global Evaluation, the Hamilton Rating Scale for Anxiety, the Marks-Sheehan Phobia Scale, the Montgomery-Asberg Depression Rating Scale, and the Sheehan Disability Scale. RESULTS: Comparisons with placebo revealed significant superiority of paroxetine (20-60 mg/day) and clomipramine (50-150 mg/day) on nearly all outcome measures. On most measures, paroxetine also showed higher efficacy than cognitive therapy. With few exceptions, cognitive therapy did not differ significantly from placebo. The number of subjects becoming panic-free (66%) was higher and the onset of action was faster in the paroxetine-treated group. Treatment with cognitive therapy yielded the highest drop-out rate (26%). CONCLUSION: In this short-term study assessing treatment of panic disorder and agoraphobia, paroxetine and clomipramine were consistently superior to pill placebo, whereas cognitive therapy was superior on only a few measures.

Adolescent↗
PubMed1999

Max interacting protein 1: loss of heterozygosity is frequent in desmoplastic melanoma.

Max interacting protein 1 (MXI1), a negative regulator of myc oncoprotein with tumor suppressor properties, has been mapped to chromosome 10q24-25. MXI1 gene loss, demonstrated by loss of heterozygosity (LOH) analysis (allelic imbalance), is a frequent event in astrocytomas and other forms of glial neoplasia. Development and progression of malignant melanoma likely involves several cooperative oncogene/tumor suppressor gene alterations, many of which remain to be elucidated. We sought to discover whether desmoplastic melanoma (DM) exhibited MXI1 LOH. Archival fixative treated tissue was used for genotyping; this necessitated a microdissection-based molecular approach uniquely designed for minute tissue samples. Nineteen formalin-fixed tissue samples from 11 patients representing primary, locally recurrent, and metastatic DM were available for study. In each case, normal and neoplastic tissue was microdissected under stereomicroscopic observation as a basis for genetic analysis. We identified MXI1 LOH in neoplastic tissue by observing allelic imbalance for a microsatellite repeat polymorphism in the 3' nontranslated region of the MXI1 gene in subjects shown to be informative. Colorectal adenocarcinoma (n = 21) and astrocytomas (n = 19) were similarly analyzed, serving as negative and positive controls, respectively, for MXI1 LOH. Five of 11 DMs in subjects informative for the MXI1 microsatellite manifested MXI1 allelic imbalance consistent with tumor suppressor LOH. Genotype fidelity with respect to MXI1 status was present in two patients from whom primary and recurrent tumor was available for comparative analysis. We found that MXI1 LOH was independent of tumor stage and survival. MXI1 LOH seems to be a relatively frequent and early event in DM development and progression, consistent with neuroectodermal histogenesis of the neoplasm.

Adult↗
PubMed1998

Predictability, controllability, and fear of symptoms of anxiety in epinephrine-induced panic.

BACKGROUND: Psychological manipulations (supplied information, safety cues) may influence panic rates during pharmacologic challenge tests in subjects with panic disorder (PD). Psychological panic models assume that fear of stress-related bodily sensations is central to the etiology of PD. METHODS: Prior to infusion of epinephrine, 50 subjects with PD were randomly assigned to one out of four experimental conditions: with or without extensive information and with or without external control, according to a 2 x 2 design. The panic rate was hypothesized to be lower in subgroups possessing extensive information and/or control. Fear of bodily sensations was used as a predictor. RESULTS: Thirty-four out of 50 patients (68%) panicked during the infusion. Subjects who received extensive information were marginally less likely to panic, but manipulation of control did not influence panic rates. Panickers did not differ from nonpanickers in measures of fear of fear. Anxiety sensitivity best predicted baseline anxiety and cognitive symptom scores, but was not associated with other outcome measures in panickers. Only baseline partial pressure of CO2 discriminated between panickers and nonpanickers. CONCLUSIONS: Manipulating external safety cues appears to be of limited value in modulating responses to epinephrine challenge. Together with our finding that fear of anxiety symptoms does not predict panic rates, these data argue against "fear of fear" as a key mechanism in epinephrine-induced panic.

Adult↗
PubMed1998

p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma.

BACKGROUND: The ability to predict biologic behavior and treatment responsiveness would be a valuable asset in the multimodality approach to esophageal carcinoma. The authors examined whether alterations of the p53 gene correlate with clinicopathologic parameters, response to preoperative chemotherapy/radiotherapy, and outcome in patients with esophageal carcinoma. METHODS. Histopathologic/genetic analysis of p53 was performed on formalin fixed, paraffin embedded tissues. Tissue sections were stained immunohistochemically for p53 protein followed by topographic genotyping comprised of polymerase chain reaction amplification and direct sequencing of p53 exons 5-8. All patients received induction chemotherapy (5-fluorouracil, cisplatin, and alpha-interferon) and concurrent external beam radiotherapy (4500 centigrays) followed by resection. RESULTS: p53 analysis performed on 42 tumors from patients with potentially resectable esophageal carcinoma revealed 25 of the 42 tumors (59.5%) to be p53 immunopositive; however, only 17 of the 42 tumors (40.5%) were proven to contain p53 point mutational damage in exons 8 (n=5), 5 (n=5), 7 (n=4), and 6 (n=3). Eight cases were weakly immunopositive and had no genotype mutation suggesting hyperexpression of normal wild-type p53. Genotyping also identified two immunonegative cases with deletion-type mutations (exons 5 and 6). Tissue samples collected before and after chemotherapy/radiotherapy exhibited fidelity in p53 mutational genotype in all cases. The presence of a p53 point mutation positively correlated with pTNM stage (P=0.003) and residual disease in the resected specimen (P=0.01). Moreover, survival of patients with p53 mutations was significantly lower than that of patients without mutations (overall survival of 21.6 months vs. 40 months; P=0.0038; and disease free survival of 14.1 months vs. 38 months; P=0.0004). CONCLUSIONS: Histopathologic/genetic analysis is a better determinant of p53 mutational damage than immunohistochemistry alone and can be used as a prognostic marker for esophageal carcinoma. p53 genotyping may define a subset of patients who respond to chemotherapy/radiotherapy and may predict who potentially benefits from multimodality therapy.

Adult↗
PubMed1998

NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics.

BACKGROUND: Both diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, in particular among the elderly. The use of NSAIDs may decrease the efficacy of diuretics and induce congestive heart failure (CHF) in patients treated with diuretics. OBJECTIVE: To investigate the risk of CHF associated with combined use of diuretics and NSAIDs in patients older than 55 years. METHODS: We conducted a study in a base cohort of 10,519 recipients of diuretics and NSAIDs identified in the PHARMO database during the period from 1986 through 1992. The incidence density of hospitalizations for CHF during exposure to both diuretics and NSAIDs (index) was compared with that during exposure to diuretics only (reference). RESULTS: We found an overall increased risk of hospitalization for CHF during periods of concomitant use of diuretics and NSAIDs compared with use of diuretics only (crude relative risk, 2.2; 95% confidence interval, 1.7-2.9). After adjusting for cofactors including age, sex, history of hospitalization, and drug use, a 2-fold increased risk remained (relative risk, 1.8; 95% confidence interval, 1.4-2.4). CONCLUSION: Use of NSAIDs in elderly patients taking diuretics is associated with a 2-fold increased risk of hospitalization for CHF, especially in those with existing serious CHF.

Aged↗
PubMed1998

Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components.

Female genital tract carcinosarcomas (FGTCS) are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. Histogenesis of FGTCS centers on two theories: (1) simultaneous formation of independent tumors (biclonal theory), (2) multidirectional differentiation of a single neoplasm (monoclonal theory). In an attempt to resolve this histogenetic controversy, we determined the presence, specific genotype, and timing of p53 mutational change in each component of FGTCS using a topographic genotyping (TG) approach. We selected 43 FGTCS from the files of Magee-Womens Hospital, Pittsburgh, and initially immunostained them for p53 protein. Strong p53 immunopositivity was detected in 35 (82%) of 43 tumors. Subsequently, topographic genotyping (TG) was performed on a subset of nine immunopositive tumors with sufficiently distinct malignant components to enable effective sampling. All nine tumors showed point mutations in p53 exons 5 through 8. In each case, the identical point mutational genotype was present in both components. Furthermore, in all nine cases mutations were present with loss of the wild-type allele. P53 gene mutation is a frequent event in progression of FGTCS. Of importance, both p53 mutation and allelic loss occur before the differentiation into separate epithelial and mesenchymal malignant components. These molecular findings strongly support monoclonal, multidirectional histogenesis of FGTCS.

Base Sequence↗
PubMed1998

Security in perspective; luxury or must?

In this paper, security in health information systems is put into perspective. The further penetration of information technology into health care is discussed and it is concluded that information systems have already become a vital component, not only for the logistics of the health care institution but also for the rendering of care and cure. Health care depends heavily on adequate data, so availability and integrity are equally important. In view of the sensitive nature of many patient data, the importance of confidentiality was recognised long before computers were invented. For widespread use of IT in health care it is of vital importance that computers can be trusted in respect of confidentiality. This paper emphasises the need to pay attention to security and suggests a responsible approach with implementation of both technical and organisational measures.

Computer Security↗
PubMed1998

Usage patterns of benzodiazepines in a Dutch community: a 10-year follow-up.

Only a few longitudinal studies have addressed benzodiazepine use over time. We therefore conducted a 10-year follow-up study (1983-1992) on usage patterns of benzodiazepines in a Dutch community of 13 500 people. Use decreased during the time of the study. Twelve (1983) to ten (1992) percent of the inhabitants was a recipient at least once a year of a benzodiazepine prescription. The use by gender showed more women using more prescriptions as men. Women were not prescribed more DDDs per prescription as men. Individual benzodiazepines showed differences in use by gender. Use increased with age among both women and men. Most of the users were 55 years or older. One out of three patients was either an incidental user (1-30 days use in one calendar year), a regular (31-180 days), or a long term user (more than 180 days). The use of long half-life hypnotics decreased, the use of the short half-life ones showed an increase. Behind a stable overall trend we found strong fluctuations in use of individual benzodiazepines.

Adult↗
PubMed1998

Measurement of patient compliance.

The compliance of 91 diabetic patients using oral antidiabetics was studied. Patient compliance was measured using four different methods. Patients received their medication in a Medication Event Monitoring System (MEMS)-container. Each time the patient went back to the pharmacy for refill prescriptions, the number of tablets left in the container were counted. Pharmacy records were used to study the number of days of delay in getting the next refill. At the end of the study, a questionnaire was sent to every patient. Using MEMS as a standard, the results show that pill count and refill data overestimate the compliance of this group of patients. The MEMS data also show that the compliance data using only the number of tablets may be biased, because of possible overconsumption. Pill count does not show a correlation with compliance as measured by MEMS. The relation between compliance as measured with MEMS and refill compliance is weak.

Adult↗
PubMed1998

Undertreatment of hypertension in a population-based study in The Netherlands.

OBJECTIVE: To estimate the level of undertreatment of hypertension in a population-based study by taking into account the co-existence of additional cardiovascular risk factors in untreated hypertensives, uncontrolled blood pressure among pharmacologically treated hypertensives and within-person variability in blood pressure and total cholesterol. DESIGN: Cross-sectional. SETTING: Two population-based surveys on cardiovascular disease risk factors conducted during 1987-1995 in The Netherlands. PARTICIPANTS: 56 026 men and women aged 20-59 years. MAIN OUTCOME MEASURES: Prevalence of hypertension, of treatment and of undertreatment of hypertension. Undertreated hypertensives were those who were treated pharmacologically, but whose blood pressure was still elevated and those who inappropriately received no medication for the treatment of hypertension. RESULTS: During the past decade in The Netherlands, 30% of the hypertensive women and 47% of the hypertensive men aged 20-59 years were undertreated for hypertension. In both men and women treated pharmacologically, 42 and 29%, respectively, still had elevated blood pressure levels. Of those hypertensive men and women not treated pharmacologically, 53 and 34%, respectively, should have been treated when additional cardiovascular risk factors were taken into account Among those diagnosed but untreated for hypertension, 58 and 31% of the men and women, respectively, should have been treated pharmacologically. CONCLUSION: A considerable proportion of hypertensives were undertreated for hypertension. To decrease the undertreatment of hypertension, it is necessary to obtain better control of blood pressure in patients already being treated, increase the detection of hypertension and improve adherence to the current guidelines.

Adult↗
PubMed1998

Sex differences in antihypertensive drug use: determinants of the choice of medication for hypertension.

OBJECTIVE: To describe and explain sex differences in antihypertensive drug use. DESIGN AND METHODS: From 1987 to 1995, two cross-sectional population-based surveys of cardiovascular disease risk factors in The Netherlands were carried out among 56026 men and women aged 20-59 years. Polytomous logistic regression modelling was used to adjust for potential confounders of the association between sex and use of different antihypertensive drugs. RESULTS: The response rate was 40% for men and 46% for women. Of these respondents, 40% (1041) of the hypertensive men and 59% (1403) of the hypertensive women were being treated pharmacologically; 57% (595) of the treated men and 54% (760) of the treated women were on monotherapy for hypertension with a diuretic (men 14.8%, women 37.2%), a beta-blocker (men 59.0%, women 45.3%), a calcium antagonist (men 8.6%, women 5.0%) or an angiotensin converting enzyme inhibitor (men 17.7%, women 12.5%). Among those on monotherapy for hypertension, women were less likely than men to be using a beta-blocker [prevalence odds ratio (POR), female/male=0.34; 95% confidence interval (CI) 0.24-0.47], a calcium antagonist (POR=0.27, 95% CI 0.15-0.48) or an angiotensin converting enzyme inhibitor (POR=0.34, 95% CI 0.22-0.52) than a diuretic. These sex differences persisted after adjustment for all factors that could have influenced the choice of these antihypertensive drugs (indications and contra-indications for the four antihypertensive drug classes). The sex differences in antihypertensive drug use were smaller among hypertensives with a history of cardiovascular disease (adjusted PORs, female/male, for beta-blockers, calcium antagonists and ACE inhibitors, respectively, compared to diuretics were 0.80 with 95% CI 0.20-3.24, 0.40 with 95% CI 0.10-0.48 and 0.64 with 95% CI 0.12-3.39) than among those without such a history. CONCLUSIONS: The different patterns of antihypertensive drug use among hypertensive men and women seem irrational, and cannot be explained by factors known to influence antihypertensive drug choice. Among hypertensives with a history of cardiovascular disease, the sex differences were smaller than among those without such a history. Further research is required to explain the sex differences in the choice of antihypertensive drug by prescribers, and to investigate the consequences of these differences for long-term patient outcomes.

Adult↗
PubMed1998

Follow-up on the treatment of panic disorder with or without agoraphobia: a quantitative review.

We conducted a meta-analysis to update the knowledge of long-term efficacy of different treatments in panic disorder with or without agoraphobia. Included were 68 studies pertaining to 106 treatment conditions and 1346 patients. Effect sizes Cohen's d were calculated within the treatment conditions at posttest and at follow-up for panic and agoraphobia. A comparison was made between six treatments: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. The mean (+/- SD) duration of the follow-up period was 62 +/- 89 weeks. In the majority of the studies (84%), follow-up had a naturalistic character. The lack of information about treatments received between posttest and follow-up limits the interpretation of the results. For all conditions, the treatment gains at posttest were maintained during the follow-up period. The mean (+/- SD) d for panic was 1.11 +/- 0.70 at posttest and 1.28 +/- 0.61 at follow-up; for agoraphobia, the mean d at posttest was 1.36 +/- 1.10 and at follow-up it was 1.41 +/- 0.82. Significant differences were found in efficacy on agoraphobic measures at follow-up between the combination of antidepressants and exposure in vivo versus psychological panic management, exposure in vivo, and the combination of psychological panic management and exposure. Overall, the data suggest that different treatment options for panic disorder with or without agoraphobia are effective at both posttest and follow-up. Research on long-term treatment, discontinuation of therapies, and interventions between posttest and follow-up need more attention, for pharmacotherapy as well as psychotherapy.

Agoraphobia↗
PubMed1998

Malignant Transformation in Sinonasal Papillomas Is Closely Associated With Aberrant p53 Expression.

Background: Sinonasal papillomas are generally benign lesions that arise from the lining of the nasal or paranasal sinuses. Occasionally, however, they may undergo malignant change, an event that is poorly understood. To elucidate the possible molecular basis of this transformation, a series of these lesions were examined for abnormal p53 protein expression and for mutations in the genes of exons 5-8. Methods and Results: Eleven cases of sinonasal papillomas (seven with associated carcinoma) were analyzed immunohistochemically for overexpression of p53 protein, as were three cases of squamous carcinoma. Genetic analysis of exons 5-8 was performed via topographic genotyping of representative tissue and polymerase chain reaction amplification. All seven papillomas with associated carcinoma showed evidence of aberrant function of the p53 gene, as did the three squamous cell carcinomas. Several exhibited point mutations resulting in missense codons. One case possessed a nonsense mutation and was immunonegative. Conclusions: p53 gene mutation appears to be closely associated with malignant transformation in sinonasal papillomas, and genotyping of archival tissues is useful in the evaluation of malignant or potentially malignant lesions.

Journal Article↗
PubMed1998

Quality management in the doctor's consulting room.

Clinical research and the measurement of quality in healthcare have similar properties. Clinical research is generally restricted to university and teaching hospitals because of it's time consuming nature while quality management and subsequent quality measurement are of interest to all medical doctors. To serve both purposes a Kaplan Meier satellite module was developed as an add-on to a medical workstation. Kaplan Meier survival statistics has interesting possibilities as a clinical tool for the measurement and graphic visualisation of quality of care. It does express the clinical behaviour of a patient population in terms of cumulative survival, patency or any other binary phenomenon. A vascular surgeon collected cumulative patency data on 340 vascular reconstructions with this Kaplan Meier module within 6 months without any perceptable influence on the normal outpatient clinic routines. The module is easy to operate, easy to maintain and very adaptable to any clinical question.

Databases, Factual↗
PubMed1997

K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer patients.

K-ras gene mutations have been reported as early events in colorectal tumorigenesis, but their role in tumor initiation and development is still unclear. To analyze and compare K-ras mutational patterns between colorectal tissues at different stages of tumor progression in individual patients, 65 colorectal tissue samples, including carcinoma, adenoma, histologically normal mucosa, submucosal muscularis propria, and histologically normal mucosa distant from tumor, were obtained from 13 patients with colorectal cancer. In addition, normal mucosal tissues obtained from four normal individuals were analyzed. Each of the 13 tumors was shown previously to harbor a mutation in either codon 12 or 13 of the K-ras gene by direct sequencing. These tissues were reanalyzed, using the recently established mutant allele enrichment + denaturing gradient gel electrophoresis method, which can detect one mutant allele in 10(4)-10(5) normal alleles, thus allowing for the analysis of infrequent cells bearing mutations against the background of wild-type cells. No K-ras codon 12 mutation was detected by this method in the histologically normal mucosal tissues sampled at the margin of resection distant from the tumor or in those obtained from four normal individuals. On the other hand, these mutations were detected in 9 of 10 adenoma and 6 of 10 mucosa samples from 10 patients with known K-ras codon 12 mutations, and also in 2 of 3 carcinoma, 2 of 3 adenoma, and 1 of 3 mucosa samples obtained from 3 patients with known K-ras codon 13 mutations. Thus, K-ras codon 12 mutations were found to occur with a high frequency (53.8%) in histologically normal mucosa adjacent to tumors of patients with K-ras mutation-positive colorectal cancer, suggesting that they may be useful biomarkers for early detection of colorectal cancer. Furthermore, multiple K-ras mutations were found in tissues of nearly half of the 13 patients, indicating that distinct evolutionary subclones may be involved in the development of tumor in some patients with colorectal cancer.

Adenoma↗