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Biomedical subjects

H Houben

Publications and source records attributed to H Houben.

At least 19 recordsLinked to original sources

Performance of various criteria sets in patients with inflammatory back pain of short duration; the Maastricht early spondyloarthritis clinic.

AIM: To describe how patients presenting with inflammatory back pain (IBP) of short duration can be classified by different sets of classification criteria for spondyloarthritis (SpA) and ankylosing spondylitis, and which clinical and imaging features are of discernible importance. METHODS: 68 patients with IBP of a maximum of 2 years' duration were included in the early spondyloarthritis cohort. Detailed history, clinical examination and imaging of sacroiliac joints by plain radiography and magnetic resonance imaging (MRI) were obtained. The Berlin criteria set for SpA that has a prominent place for MRI and human leucocyte antigen B27 was used to quantify the relative contribution of MRI in classifying SpA. RESULTS: 14 of the 68 patients had ankylosing spondylitis according to the modified New York criteria, 57 patients fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for SpA, 48 patients fulfilled the Amor criteria for SpA (43 patients fulfilled both criteria sets) and 44 patients fulfilled the Berlin criteria for SpA. Only four patients did not fulfil any criteria set; 36 patients fulfilled ESSG, Amor and Berlin criteria. The 14 patients with ankylosing spondylitis fulfilled all three SpA criteria sets. CONCLUSION: Among our selected cohort of patients with early IBP, the prevalence of SpA according to three different criteria sets is high. The ESSG criteria were the most sensitive, followed by the Amor criteria and the Berlin criteria. The modified New York criteria for ankylosing spondylitis appeared to be the most specific. In this cohort, the contribution of MRI and human leucocyte antigen B27 to purely clinical criteria in making a diagnosis of axial SpA was limited.

Algorithms↗

Combining information obtained from magnetic resonance imaging and conventional radiographs to detect sacroiliitis in patients with recent onset inflammatory back pain.

OBJECTIVE: To compare the contribution of changes on magnetic resonance imaging (MRI) and conventional radiography (CR) in the sacroiliac joints of patients with recent onset inflammatory back pain (IBP) in making an early diagnosis of spondyloarthritides. METHODS: The study involved 68 patients with IBP (38% male; mean (SD) age, 34.9 (10.3) years) with symptom duration less than two years. Coronal MRI of the sacroiliac joints was scored for inflammation and structural changes, and pelvic radiographs were scored by the modified New York (mNY) grading. Agreement between MRI and CR was analysed by cross tabulation per sacroiliac joint and per patient. RESULTS: A structural change was detected in 20 sacroiliac joints by MRI and in 37 by CR. Inflammation was detected in 36 sacroiliac joints by MRI, and 22 of these showed radiographic sacroiliitis. Fourteen patients fulfilled the mNY criteria based on CR. Classification according to the modified New York criteria would be justified for eight patients if it was based on MRI for structural changes only, for 14 if it was based on structural changes on CR, for 14 (partly) different patients if it was based on inflammation on MRI only, for 16 if it was based on inflammation and structural changes on MRI, for 19 if it was based on inflammation on CR combined with MRI, and for (the same) 19 if it was based on inflammation and structural damage on CR combined with MRI. CONCLUSIONS: CR can detect structural changes in SI joints with higher sensitivity than MRI. However, inflammation on MRI can be found in a substantial proportion of patients with IBP but normal radiographs. Assessment of structural changes by CR followed by assessment of inflammation on MRI in patients with negative findings gives the highest returns for detecting involvement of the SI joints by imaging in patients with recent onset IBP.

Adult↗

The role of a computerised case-based testing procedure in practice performance assessment.

INTRODUCTION: For postgraduate training of doctors there is a need for valid and reliable instruments to assess their daily performance. Various instruments have been suggested, some of which use incognito simulated patients (SPs). These methods are resource intensive. Computerised Case-based testing (CCT) is logistically simpler and may still predict performance well. The research question was to evaluate the predictive validity of CCT for performance. METHODS: Seventeen rheumatologists were each visited by eight incognito SPs presenting various rheumatological complaints, and scoring the performance of the rheumatologists using a predefined checklist. From this checklist a panel of experts identified essential items. In addition the rheumatologists sat a CCT test containing 55 cases with a total of 121 items. RESULTS: Negative correlations were found between the SP scores and the CCT scores. This was unexpected. Therefore, background variables on experience were used to compare both methods. The correlation between these and CCT were high and positive and with the SP scores high and negative. This pattern did not differ when using the essential items of the checklist. Reliabilities of the SP scores were markedly high. DISCUSSION: Although CCT was not predictive of SP scores, it was related to working experience. There are good reasons to assume that although SP-scores were more authentic, they were less valid than CCT scores, mainly because they focussed more on thoroughness than on efficiency in data gathering. The results underpin the assumption that for valid performance assessment the most important issue is what information about the candidate is collected and now how authentic the method is.

Clinical Competence↗

Psoriatic arthritis: performance of rheumatologists in daily practice.

OBJECTIVES: To assess, using standardised patients (SPs), how rheumatologists diagnose psoriatic arthritis, whether the diagnostic efficiency is influenced by specific characteristics of the rheumatologists, and to study the relationship with costs. METHODS: Twenty three rheumatologists were each visited by one of two SPs (one male, one female) presenting as a patient with psoriatic arthritis. SPs remained incognito for all meetings for the duration of the study. Immediately after the encounter, SPs completed case-specific checklists on the medical content of the encounter. Information on ordered laboratory and imaging tests was obtained from each hospital. RESULTS: Fourteen rheumatologists diagnosed psoriatic arthritis correctly. They inspected the skin for psoriatic lesions more often than those rheumatologists who established other diagnoses. Rheumatologists diagnosing psoriatic arthritis spent more on additional laboratory and imaging investigations. These were carried out after the diagnosis to confirm it and to record the extent and severity of the disease. No differences in type of practice, number of outpatients seen each week, working experience, or sex were found between rheumatologists who made the correct diagnosis and those who made other diagnoses. The correct diagnosis was more often missed by rheumatologists who saw the male SP, who presented with clear distal interphalangeal DIP joint arthritis only, causing confusion with osteoarthritis of the DIP joints. CONCLUSION: There is a considerable amount of variation in the delivery of care among rheumatologists who see an SP with psoriatic arthritis. Rheumatologists focusing too much on the most prominent features (DIP joint arthritis) sometimes seem to forget "the hidden (skin) symptoms".

Adult↗

Rhemulatologists' performance in dailiy practice.

OBJECTIVE: To assess rheumatologists' performance for 8 rheumatologic conditions and to explore possible explanatory factors. METHODS: After written informed consent was obtained, 27 rheumatologists (21% of all Dutch rheumatologists) practicing in 16 outpatient departments were each visited by 8 incognito "standardized patients" (SPs). The diagnoses of these 8 cases account for about 23% of all new referred patients in the Netherlands. Results for ordered lab tests as well as real radiographs with corresponding results from a radiologist were simulated. Information from the visits was obtained from the SPs, who completed predefined case-specific checklists, and by collecting data on resource utilization. Feedback was provided. RESULTS: Altogether 254 encounters took place, of which 201 were first visits and 53 were followup visits. SPs were unmasked twice during a visit. There was considerable variation in resource utilization (lab tests and imaging) between cases and between rheumatologists. Mean costs per rheumatologist ranged from US $ 4.67 to $ 65.36 per visit for lab tests and from US $ 33.15 to $ 226.84 per visit for imaging tests. No significant correlations were seen between resource utilization costs and number of years of clinical experience or performance on checklist scores. Rheumatologists with longer experience had lower total item checklist scores (r = -0.47; P < 0.05). CONCLUSION: A considerable variation in resource utilization was found among 27 Dutch rheumatologists. The information obtained is an excellent source for discussion on the appropriateness of care.

Adult↗

Minimal clinically important difference in radiological progression of joint damage over 1 year in rheumatoid arthritis: preliminary results of a validation study with clinical experts.

To determine the minimal clinically important difference (MCID) between hand and foot films with a 1 year interval assessed with the Sharp/van der Heijde or Larsen/Scott scoring method. Progression scores of the 2 methods were compared with the opinion of an international expert panel on clinical relevance of radiological joint damage in 4 predefined clinical settings. The expert panel consisted of 3 rheumatologists, who evaluated 46 pairs of hand and foot films, taken with 1 year intervals, of patients with early rheumatoid arthritis. Receiver operating characteristics curves analyzed the accuracy of different threshold values (progression scores) of the 2 scoring methods to detect the presence or absence of clinically important difference, as defined by the expert panel as external criterion. The threshold value with the highest accuracy was subsequently chosen as the score representing the MCID. Five Sharp/van der Heijde units and 2 Larsen/Scott units were the best cutoffs. The accompanying sensitivities ranged from 77% to 100% for the Sharp/van der Heijde method and from 73% to 84% for the Larsen/Scott method for the 4 clinical settings. The specificities were between 78% and 84% for the Sharp/van der Heijde method and between 74% and 94% for the Larsen/Scott method. The smallest progression score that can be detected apart from interobserver measurement error, the smallest detectable difference (SDD), was equal to or larger than the calculated MCID, 5 Sharp/van der Heijde units and 6 Larsen/Scott units in our study, if the mean progression scores of the same 2 observers were used. The SDD is a conservative estimate of the MCID; our panel rated progression at or below this level as clinically significant.

Arthritis, Rheumatoid↗

Developing case-specific checklists for standardized-patient-based assessments in internal medicine: A review of the literature.

PURPOSE: To review the literature on the methods used in writing case-specific checklists for studies of internal medicine physicians' performances that were assessed by standardized patients. METHOD: The authors searched Medline, Embase, Psychlit, and ERIC for articles in English published between 1966 and February 1998. The following search string was used: "[(standardi(*) or simulat(*) or programm(*)) near (patient(*) or client(*) or consultati(*))] and internal medicine." The authors then searched the reference lists of papers retrieved from the database searches, as well as those from seven proceedings of the International Ottawa Conference on Medical Education and Assessment. RESULTS: The procedure yielded 29 relevant articles: database searches yielded 14 published reports dealing with case-specific checklists, 11 articles were culled from the reference lists of these papers, and the Ottawa Conference proceedings yielded four articles. Only 12 articles reported specifically on the development of checklists. In general, there were three sources used for developing checklists: panels of experts, the investigators themselves, and responses from expert physicians to written protocols. No article indicated that researchers had relied exclusively on data from the literature to compose their checklists. Only three articles indicated that literature sources had informed their checklist development. All articles except one relied on explicit criteria for the inclusion of items on the checklists. In 21 of the 29 articles, the checklists had been scored by SPs, but the scoring of specific items on the checklists varied according to the purpose of the SP-physician encounter. Only four of the articles made the checklists available or indicated that the checklists could be obtained from the authors. CONCLUSION: The development of case-specific checklists for SP examinations of physicians' performance has received little attention. To judge the validity of studies of physicians' performances that use SPs, the development processes for the checklists need to be more fully described to enable readers to evaluate the validity and reliability of the studies.

Clinical Competence↗

Evolution of the Martian water cycle.

The current Martian water cycle is extremely asymmetric, with large amounts of vapor subliming off a permanent north polar water ice cap in northern summer, but with no apparent major source of water vapor in the southern hemisphere. Detailed simulations of this process with a three-dimensional circulation model indicate that the summertime interhemispheric exchange (Hadley cell) is very much stronger than transport by eddies in other seasons. As a result, water ice would be distributed globally were it not for the buffering action of regolith soil adsorption which limits the net flux of water vapor off the north polar cap to amounts that are insignificant even on the scale of thousands of years. It has been suggested that the polar layered deposits are the result of exchange on these long time scales, driven by changes in Martian orbital parameters. We therefore are conducting simulations to test the effect of varied orbital parameters on the Martian water cycle. We find that when the perihelion summer pole is charged with a polar water ice cap, large quantities of water are quickly transfered to the aphelion summer pole, setting up an annual cycle that resembles the present one. Thus, the adsorptivity of the Martian regolith may be in the narrow range where it can limit net transport from the aphelion but not the perihelion pole.

Adsorption↗

Autoradiographic demonstration of 125I-Tyr4-bombesin binding sites on rat anterior pituitary cells.

Because several direct effects of bombesin related peptides on pituitary hormone release have been demonstrated, we chose to study the presence of bombesin binding sites in the adult male rat anterior pituitary in aggregate cell culture by autoradiographic localization of 125I-tyrosine4-bombesin (125I-Tyr4-BBN) binding and immunocytochemical localization of the anterior pituitary hormones. When aggregates were cultured in medium without hormonal supplements, the number of cells with detectable 125I-Tyr4-BBN binding was below 1%. In cell aggregates cultured in the presence of 1 nM estradiol (E2) 125I-Tyr4-BBN binding was detected on 5.4 +/- 0.8% of the cells after redispersion and on 5.8 +/- 1.1% of the cells in sections of paraffin embedded aggregates. The binding cell types were mainly lactotrophs and somatotrophs. The binding of 125I-Tyr4-BBN (3 or 5 nM) was specific because it was inhibited by the addition of an excess of unlabelled Tyr4-BBN or the bombesin receptor antagonist L686,095. In aggregates cultured in the presence of 1 nM E2 and 4 nM dex, the percentage of cells with detectable 125I-Tyr4-BBN binding was significantly lower than that in aggregates cultured in the presence of 1 nM E2 alone. Binding on somatotrophes almost completely disappeared. The present data show that specific 125I-Tyr4-BBN binding sites are present on anterior pituitary cells, are detectable mainly on a small subpopulation of lactotrophs and somatotrophs, and are affected by hormonal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bioactive peptides in anterior pituitary cells.

The anterior pituitary (AP) has been shown to contain a wide variety of bioactive peptides: brain-gut peptides, growth factors, hypothalamic releasing factors, posterior lobe peptides, opioids, and various other peptides. The localization of most of these peptides was first established by immunocytochemical methods and some of the peptides were localized in identified cell types. Although intracellular localization of a peptide may be the consequence of internalization from the plasma compartment, there is evidence for local synthesis of most of these peptides in the AP based on the identification of their messenger-RNA (mRNA). In several cases the release of the peptide from the AP cell has been shown and regulation of synthesis, storage and release have also been described. Because the amount of most of the AP peptides is very low (except for POMC peptides and galanin), endocrine functions are not expected. There is more evidence for paracrine, autocrine, or intracrine roles in growth, differentiation, and regeneration, or in the control of hormone release. To demonstrate such functions, in vitro AP experiments have been designed to avoid the interference of hypothalamic or peripheral hormones. The strategy is first to show a direct effect of the peptide after adding it to the in vitro system and, secondly, to explore if the endogenous AP peptide has a similar action by using blockers of peptide receptors or antisera immunoneutralizing the peptide.

Animals↗

Expression of the genes encoding bombesin-related peptides and their receptors in anterior pituitary tissue.

The bombesin-related peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been demonstrated in the anterior pituitary (AP) on an immunological basis. We studied the presence of mRNAs for these peptides and for their receptors by RNAse protection assay using fresh adult male rat AP, AP cell reaggregates cultured in the presence of estradiol and the rat AP derived GH3 cell line. In total RNA from fresh AP we detected high amounts of NMB mRNA and much smaller amounts of GRP mRNA, while finding a weak signal for GRP-receptor (GRP-R) and NMB-receptor (NMB-R) mRNAs. In total RNA from the reaggregate cell cultures we detected high levels of NMB mRNA as well as a strong signal for GRP-R mRNA. Finally, in GH3 cells, high levels of NMB mRNA and GRP-R mRNA were found, while GRP mRNA and NMB-R mRNA remained undetectable even in high amounts (200 micrograms) of total RNA. We conclude that mRNAs encoding both bombesin-related peptides and each of the mRNAs encoding their receptors are expressed in rat AP tissue. NMB mRNA is more prominent than GRP mRNA in all AP-like tissues examined (fresh AP, estradiol-treated reaggregate AP cell cultures and GH3 cells). NMB-R mRNA and GRP-R mRNA are both present in low levels in fresh AP whereas the GRP-R mRNA is predominant in GH3 cells and estradiol treated AP reaggregate cell cultures. Compared to fresh AP tissue, NMB mRNA and GRP-R mRNA expression is enhanced in estradiol-treated reaggregate cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Negative regulation by dexamethasone of the potentiation of neuromedin C-induced growth hormone and prolactin release by estradiol in anterior pituitary cell aggregates.

The bombesin-like peptide neuromedin C (NMC) stimulated the release of growth hormone (GH) and prolactin (PRL) from adult male rat anterior pituitary cell aggregates cultured in serum-free medium. This effect, particularly on GH release, was significantly increased when the cells were cultured in the presence of estradiol (E2). The GH response to NMC was not affected by 4 nM dexamethasone (Dex) but was enhanced in the presence of 80 nM Dex. However, the strong stimulatory action of E2 on the GH response to NMC was completely abolished by 4 nM Dex. In contrast, the PRL response to NMC was reduced by 4 nM Dex and this to a proportionally similar extent in the presence or absence of E2. The present data show that glucocorticoids can be both positive and negative regulators of the same response system.

Animals↗

Evidence for the presence of gastrin-releasing peptide immunoreactivity in rat anterior pituitary corticotrophs and lactotrophs, AtT20 cells, and GH3 cells: failure to demonstrate participation in local control of hormone release.

Using antisera raised against the N-terminal (1-16) or the C-terminal part of the bombesin (BBN)-like peptide gastrin-releasing peptide (GRP) and against the C-terminus of pro-GRP, GRP- and pro-GRP-like immunoreactivity (IR) was detected by immunostaining in freshly dispersed rat anterior pituitary (AP) cells and in reaggregate AP cells cultured in serum-free medium. Depending on the antiserum used, 6.4 +/- 0.4% to 12.4 +/- 2.7% of freshly dispersed cells were immunoreactive. Solid phase preabsorption of the antisera with the respective antigens abolished the staining. GRP-IR was detectable by double immunostaining in a subpopulation of PRL cells and ACTH-containing cells. In contrast, only very few somatotrophs, gonadotrophs, and thyrotrophs were immunoreactive, and they were much smaller than the typical mature forms of these cell types. GRP- and pro-GRP-IR were also detected in the ACTH-secreting AtT20 cell line and in the PRL- and GH-secreting GH3 cell line. GRP- and pro-GRP-IR were present in AP cell aggregates maintained in culture for 4 weeks. The finding of both GRP- and pro-GRP-IR in a subpopulation of lactotrophs and corticotrophs and their persistence in culture under serum-free conditions strongly suggest that GRP-like peptides are produced in rat AP. Although the potent GRP receptor antagonist L 686,095-001C002 effectively blocks stimulation of GH and PRL release by exogenous BBN-like peptides, it failed to affect basal GH and PRL release from perifused reaggregate AP cell cultures as well as GH and/or PRL release stimulated by epinephrine, vasoactive intestinal peptide, TRH, GH-releasing factor, and angiotensin-II or PRL release inhibited by dopamine. Thus, the latter data do not support the hypothesis often suggested that peptides endogenously present in AP cells are involved in the paracrine regulation of AP hormone secretion.

Adrenocorticotropic Hormone↗

Stimulation of growth hormone and prolactin release from rat pituitary cell aggregates by bombesin- and ranatensin-like peptides is potentiated by estradiol, 5 alpha-dihydrotestosterone, and dexamethasone.

The effect of the bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin-C (NMC), and the ranatensin-like peptides, neuromedin-B (NMB), neuromedin-B30 (NMB30), and neuromedin-B32 (NMB32), on pituitary GH and PRL release was studied in perifused anterior pituitary aggregate cell cultures from 9- to 12-week-old male rats cultured in serum-free defined medium supplemented with 0.05 nM T3 and 4 nM dexamethasone (DEX). All peptides stimulated PRL and GH release. GRP and NMC stimulated hormone release in a concentration-dependent manner between 0.1-10 nM. NMB was slightly more potent than NMB30 and NMB32, but was significantly less potent than GRP and NMC. The magnitude of the PRL response to GRP and NMC inversely correlated with that of the GH response. Cultures with relatively low PRL response levels displayed high GH responses, whereas the opposite was found in cultures with high PRL response levels. The stimulatory actions of GRP, NMC, and NMB were blocked by the bombesin receptor antagonist Leu13 psi (CH2NH) Leu14-bombesin, supporting the specificity of the findings. Addition of 1 nM estradiol (E2) to the culture medium provoked an impressive (4- to 10-fold) increase in the magnitude of the GH response to NMC without changing the EC50 value (0.5 nM). In contrast, E2 significantly decreased the stimulation of GH release by rat GH-releasing factor. In the E2-treated aggregates 3 nM NMC stimulated GH release to a comparable extent as 0.1 nM GRF. 5 alpha-Dihydrotesterone (10 and 100 nM) and DEX (80 nM) also enhanced the GH response to NMC, but to a much smaller extent than E2. E2 had also a stimulatory effect on the PRL response to NMC, particularly in cultures with a low intrinsic PRL response. The PRL response to NMC was decreased by DEX and slightly augmented by 5 alpha-dihydrotestosterone. It is concluded that bombesin- and ranatensin-like peptides have a stimulatory effect on GH and PRL release at the pituitary level. Since their action on GH release is strongly potentiated by E2 and much less so by glucocorticoids, these peptides clearly distinguish their activity and specificity from that of the protagonist releasing factor GH-releasing factor, suggesting a role in sex-related differences in GH release or in the control of GH secretion during sexual maturation.

Animals↗

Reproducibility of haemodynamic and plasma catecholamine responses to isometric exercise and mental arithmetic in normo- and hyper-tensive subjects.

1. To determine the reproducibility of a mental arithmetic stress test and a handgrip exercise test, we studied the responses of blood pressure, heart rate, forearm blood flow and plasma catecholamines on two occasions, with an interval of at least 1 week, in 24 normotensive and 22 hypertensive subjects. 2. The SE of a single observation of the percentage changes of blood pressure ranged from 3.9 to 9.3% in normotensive subjects and from 3.9 to 7.4% in hypertensive subjects in both tests. For heart rate, these values were 4.9-12.3% in the normotensive subjects and 4.8-5.7% in the hypertensive subjects. However, there was a wide individual scatter of these haemodynamic responses during both tests. The forearm blood flow, only measured during mental arithmetic, had an SE of a single observation of 33.7%. 3. In 10 normotensive subjects the SE of a single observation of the change in plasma noradrenaline was 0.16 nmol/l during handgrip exercise and 0.09 nmol/l during mental arithmetic. The corresponding values for plasma adrenaline were 0.04 and 0.05 nmol/l. 4. In conclusion, although both tests showed a rather low SE of a single observation for the blood pressure and heart rate responses in normo- and hyper-tensive subjects, there was a considerable individual variability. If related to the mean forearm blood flow responses, the SE of a single observation of the forearm blood flow response was of similar magnitude. The limited intra-individual reproducibility of both tests should be borne in mind when interpreting pharmacological intervention studies or studies evaluating sympathoadrenal reactivity in cardiovascular disorders.

Adolescent↗

Scl-86, a marker antigen for diffuse scleroderma.

More than 300 sera from patients with a connective tissue disease were analyzed with the immunoblotting technique. The presence of autoantibodies against an 86,000-mol wt marker antigen for diffuse scleroderma (Scl-86) was found in 14 out of 33 patients with scleroderma. The presence of anti-Scl-86 antibodies seemed to correlate with the diagnosis of diffuse scleroderma since they were found in 13 out of 22 diffuse scleroderma patients and in only one out of 11 patients with limited scleroderma. All scleroderma sera (33 patients' sera and 13 reference sera) were also tested for the presence of anti-Scl-70 antibodies. It was found that all anti-Scl-70 positive sera (n = 25) contained anti-Scl-86 antibody as well, suggesting a relationship between these two antigens. However, the Scl-86 antigen was shown to be an extremely insoluble nonchromosomal protein, resistant to boiling in sodium dodecyl sulfate. This contrasts with the Scl-70 antigen, which has been described as a thermolabile, soluble antigen present in the chromatin fraction. Together, our results are consistent with the idea that Scl-70 is a degradation product of Scl-86. The Scl-86 antigen is present in freshly prepared rabbit thymus, spleen, and liver nuclei as well as in nuclei from various cultured cell lines, but is not detectable in extractable nuclear antigen from rabbit thymus. In a limited retrospective study, the anti-Scl-86 antibodies were found in two sera from patients with Raynaud's phenomenon before the development of diffuse scleroderma. Therefore, it is possible that screening of patients' serum for this antibody might predict the development of diffuse scleroderma.

Animals↗