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Biomedical subjects

M Vermeulen

Publications and source records attributed to M Vermeulen.

At least 55 records · Page 3Linked to original sources
PubMed2002

Direct costs of modern treatment of aneurysmal subarachnoid hemorrhage in the first year after diagnosis.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the current direct costs of modern management of patients with aneurysmal subarachnoid hemorrhage in the first year after diagnosis. METHODS: During a 1-year period, we studied all admitted patients with subarachnoid hemorrhage from a population of 2 million people. We calculated the direct costs of treatment, which included the costs of medical and nursing care and the related travel expenses of patients. We calculated true costs for all major healthcare resources. National census data, if available, and standard charges were used to determine healthcare resource expenses. RESULTS: Hospital admissions and diagnostic and therapeutic interventions in 110 patients accounted for 85% of all costs; 64% of the total direct medical costs during admission were the medical, nursing, and overhead costs alone. Patients discharged directly to home generated 4% of the total budget, whereas admission to a nursing home accounted for the remaining 11% of the total costs. Of the diagnostic and therapeutic costs, 45% was caused by imaging and 42% by surgery or coiling. Angiography alone accounted for 52% of the total imaging costs and 24% of the total diagnostic and therapeutic costs. Prescribed medication accounted for only 3% of the total budget of diagnostic and therapeutic costs. CONCLUSIONS: Most direct costs during the first year after aneurysmal subarachnoid hemorrhage are caused by the hospital inpatient days, accounting for two thirds of the total costs generated during the first year after the initial bleeding. If new costly treatments succeed in reducing the average length of inpatient hospital stays, then progress in therapy may prove cost effective and might even be cost saving.

Cohort Studies↗
PubMed2001

[Roaming through methodology. XXXVI. Likelihood ratios and Bayes' rule].

In practice, the terms 'sensitivity' and 'specificity' are often used in a different sense to that found in textbooks. Their value depends on the composition of the groups in which the test was applied. It is rarely recognised that sensitivity and specificity change during the course of a disease. The interpretation of their value appears to be difficult. The likelihood ratio combines sensitivity and specificity, and is therefore associated with the same problems. The likelihood ratio is Bayes' rule in its simplest form: how does a given probability (in this case that of a particular disease being present) change with the addition of a single new fact (i.e., the result of a diagnostic test)? The Bayesian approach is applied in various fields but rarely in clinical practice, because the prior probability of a diagnosis is difficult to quantify. Likelihood ratios are useful when studying the diagnostic process and when teaching the diagnostic thought process. They can also be applied in the statistical interpretation of clinical trial results.

Bayes Theorem↗
PubMed2001

cAMP is involved in the differentiation of human teratocarcinoma cells.

The generation of fully differentiated post-mitotic human neuronal cells from stem cells (human teratocarcinoma (hNT2) cells) might enable the development of a co-culture model of human neurons with human Schwann cells (SCs). This co-culture model is an important tool to study formation of myelin sheaths. However, the thin process of the post-mitotic human neuronal cells formed under known culture conditions do not provide a good substrate for human SCs to start myelination. We optimized the culture conditions of these cells to obtain axons with a larger diameter. Western blotting and immunofluorescence studies were performed to confirm the neuronal status of the cells and diameter of the processes. In this study, we show that addition of cAMP-inducing factors to hNT2 cells resulted in rapid morphological changes including the development of processes with a larger diameter.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Investigation of serum response to PMP22, connexin 32 and P(0) in inflammatory neuropathies.

We investigated serological immune responses against three major peripheral nerve myelin constituents in patients with immune-mediated neuropathies. Connexin 32 (Cx32), myelin protein zero (MPZ, P(0)) and peripheral myelin protein 22 (PMP22) were produced in Chinese hamster ovary (CHO)-K1 cells. From a panel of 25 Guillain-Barré syndrome (GBS) and 24 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, only two patients showed reactivity towards Cx32 and P(0).

Animals↗
PubMed2001

Promotion of neutrophil apoptosis by TNF-alpha.

We examined the ability of TNF-alpha to modulate human neutrophil apoptosis. Neutrophils cultured with TNF-alpha alone undergo a low but significant increase in the number of apoptotic cells. More interestingly, when neutrophils were pretreated with TNF-alpha for 1-2 min at 37 degrees C and then were exposed to a variety of agents such as immobilized IgG, IgG-coated erythrocytes, complement-treated erythrocytes, zymosan, PMA, zymosan-activated serum, fMLP, Escherichia coli, and GM-CSF for 3 h at 37 degrees C, a marked stimulation of apoptosis was observed. Similar results were obtained in neutrophils pretreated with TNF-alpha for 30 min, 1 h, 3 h, and 18 h. Dose-dependent studies showed that TNF-alpha enhances neutrophil apoptosis at concentrations ranging from 1 to 100 ng/ml. In contrast to the observations made in neutrophils pretreated with TNF-alpha, there was no stimulation of apoptosis when TNF-alpha was added to neutrophils previously activated by conventional agonists. Experiments performed to establish the mechanism through which TNF-alpha promotes neutrophil apoptosis showed that neither reactive oxygen intermediates nor the Fas/Fas ligand system appear to be involved. Our results suggest that TNF-alpha plays a critical role in the control of neutrophil survival by virtue of its ability to induce an apoptotic death program which could be triggered by a variety of conventional agonists.

Annexin A5↗
PubMed2001

Non-malignant leukocytes delay spontaneous B-CLL cell apoptosis.

Malignant B cells from chronic lymphocytic leukemia (B-CLL) patients have a long survival in vivo, although, in culture, they spontaneously die by apoptosis. Here, we analyzed the capacity of accessory leukocytes to modulate apoptosis of B-CLL cells in vitro. To this end, we performed long-term cultures using total mononuclear cells (TMC) from B-CLL patients and TMC depleted from monocytes, NK cells and T lymphocytes (B-CLL cells). In all the patients studied (n = 25) the presence of accessory leukocytes markedly prolonged the survival of B-CLL cells. The anti-apoptotic effect was exerted by monocytes and, to a lesser degree, NK cells, partially through the release of soluble factors. Indeed, accessory leukocytes separated from leukemic cells by semipermeable membranes were still able to prolong B-CLL cell survival. By flow cytometric analysis we found that the protective effect of non-malignant cells was associated with delayed down-regulation of Bcl-2 expression on leukemic cells. By contrast, the expression of Fas and Fas ligand proteins was unchanged in most samples. Our findings suggest that monocytes and NK cells, by delaying leukemic cell apoptosis, may play a role in B-CLL cell accumulation in vivo.

Aged↗
PubMed2001

Medroxyprogesterone acetate enhances in vivo and in vitro antibody production.

In the present study we examine the effects of medroxyprogesterone acetate (MPA) on the specific antibody secretion to T-dependent antigens. Our results show that the in vivo administration of MPA to mice, 7 or 90 days before immunization with sheep red blood cells (SRBC), significantly enhanced both, primary and secondary antibody responses, without affecting delayed-type hypersensitivity (DTH). These effects could be counteracted by the anti-progestin onapristone or ZK 98299 (ZK) suggesting that MPA interacted with progesterone (PRG) receptors to increase B-cell response. To better understand the mechanisms involved in MPA activity we carried out cultures of splenocytes, bone marrow cells or lymph node cells from immunized mice in the presence of MPA, and evaluated the amount of antibody release to supernatants. We found that low doses of MPA (10(-9) M and 10(-10) M) significantly enhanced the in vitro production of specific immunoglobulin G (IgG) antibodies, an effect that appears to involve the interaction of the progestin with PRG receptors, as judged by the inhibition of MPA effects with ZK (10(-8) M) or RU486 (10(-9) M). These receptors were detected by flow cytometry analysis in a proportion of T lymphocytes. Because MPA did not increase the number of immunoglobulin-secreting cells, our findings suggest that MPA enhanced the capacity of individual cells to produce specific immunoglobulin.

Animals↗
PubMed2001

Diagnostic investigation of patients with chronic polyneuropathy: evaluation of a clinical guideline.

OBJECTIVE: (1) To evaluate a clinical guideline for the diagnostic investigation of patients presenting with signs and symptoms (present for longer than 6 weeks) suggesting a chronic polyneuropathy. (2) To investigate the contribution of electrophysiological studies to a focused search for aetiology in these patients. METHODS: A chart review was carried out of a consecutive group of outpatients in 1993-7 at a university department of neurology, with signs and symptoms suggesting a polyneuropathy in whom the diagnostic investigation had been carried out according to a recently introduced guideline. Diagnostic tests were performed and final diagnoses were made. RESULTS: Unnecessary investigations were carried out in 108 (51%) of 213 patients and too few tests in 23 (11%) of these patients. In 82 (48%) of the 172 patients who fulfilled the inclusion criteria neurophysiological tests did not contribute to the final diagnosis. Neurophysiological criteria for demyelination were fulfilled in only 13 (8%) of the 172 patients. CONCLUSION: In patients presenting with signs and symptoms of chronic polyneuropathy the number of tests in the diagnostic investigation can be considerably reduced. In patients with signs and symptoms of polyneuropathy, providing the clinical phenotype is typical, in the presence of diabetes mellitus, renal failure, HIV infection, alcoholism, or use of potentially neurotoxic drugs further investigations are non-contributory. The significance of electrophysiological studies in the investigation of patients with polyneuropathy is rather to separate sensorimotor neuropathies from pure sensory neuropathies than to distinguish between demyelinating and axonal neuropathies.

Chronic Disease↗
PubMed2001

Functional desensitization to isoproterenol without reducing cAMP production in canine failing cardiocytes.

To corroborate alterations in the functional responses to beta-adrenergic receptor (beta-AR) stimulation with changes in beta-AR signaling in failing cardiomyocytes, contractile and L-type Ca(2+) current responses to isoproterenol along with stimulated cAMP generation were compared among cardiomyocytes isolated from canines with tachycardia-induced heart failure or healthy hearts. The magnitude of shortening of failing cardiomyocytes was significantly depressed (by 22 +/- 4.4%) under basal conditions, and the maximal response to isoproterenol was significantly reduced (by 45 +/- 18%). Similar results were obtained when the responses in the rate of contraction and rate of relaxation to isoproterenol were considered. The L-type Ca(2+) current amplitude measured in failing cardiomyocytes under basal conditions was unchanged, but the responses to isoproterenol were significantly reduced compared with healthy cells. Isoproterenol-stimulated cAMP generation was similar in sarcolemmal membranes derived from the homogenates of failing (45 +/- 6.8) and healthy cardiomyocytes (52 +/- 8.5 pmol cAMP. mg protein(-1). min(-1)). However, stimulated cAMP generation was found to be significantly reduced when the membranes were derived from the homogenates of whole tissue (failing: 67 +/- 8.1 vs. healthy: 140 +/- 27.8 pmol cAMP. mg protein(-1). min(-1)). Total beta-AR density was not reduced in membranes derived from either whole tissue or isolated cardiomyocyte homogenates, but the beta(1)/beta(2) ratio was significantly reduced in the former (failing: 45/55 vs. healthy: 72/28) without being altered in the latter (failing: 72/28, healthy: 77/23). We thus conclude that, in tachycardia-induced heart failure, reduction in the functional responses of isolated cardiomyocytes to beta-AR stimulation may be attributed to alterations in the excitation-contraction machinery rather than to limitation of cAMP generation.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: The Very Early Nimodipine Use in Stroke (VENUS) trial was designed to test the hypothesis that early treatment with nimodipine has a positive effect on survival and functional outcome after stroke. This was suggested in a previous meta-analysis on the use of nimodipine in stroke. However, in a recent Cochrane review we were unable to reproduce these positive results. This led to the early termination of VENUS after an interim analysis. METHODS: In this randomized, double-blind, placebo-controlled trial, treatment was started by general practitioners or neurologists within 6 hours after stroke onset (oral nimodipine 30 mg QID or identical placebo, for 10 days). Main analyses included comparisons of the primary end point (poor outcome, defined as death or dependency after 3 months) and secondary end points (neurological status and blood pressure 24 hours after inclusion, mortality after 10 days, and adverse events) between treatment groups. Subgroup analyses (on final diagnosis and based on the per-protocol data set) were performed. RESULTS: At trial termination, after inclusion of 454 patients (225 nimodipine, 229 placebo), no effect of nimodipine was found. After 3 months of follow-up, 32% (n=71) of patients in the nimodipine group had a poor outcome compared with 27% (n=62) in the placebo group (relative risk, 1.2; 95% CI, 0.9 to 1.6). A treatment effect was not found for secondary outcomes and in the subgroup analyses. CONCLUSIONS: The results of VENUS do not support the hypothesis of a beneficial effect of early nimodipine in stroke patients.

Acute Disease↗
PubMed2001

Nimodipine increases fibrinolytic activity in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was first, to investigate which factor in the fibrinolytic cascade is responsible for the recently observed increase of fibrinolytic activity in patients with aneurysmal subarachnoid hemorrhage (SAH), and second, the cause of this increase. METHODS: Fibrinolytic activity and the main regulators of endogenous fibrinolytic activity, tissue plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) were measured in patients treated with and without nimodipine. RESULTS: In patients with aneurysmal SAH, fibrinolytic activity significantly increases from 2.7 IU/mL on admission to 4.2 IU/mL in week 3 (P<0.01, paired-sample t test), caused by a 1.6-fold decrease in plasma levels of PAI-1. The results also show that increased fibrinolytic activity is seen only in patients treated with nimodipine and that plasminogen activity and PAI-1 returned to baseline levels after treatment with nimodipine had been discontinued. CONCLUSIONS: The mechanism of increased fibrinolytic activity in patients with aneurysmal SAH is a decrease in the level of PAI-1, which is most likely caused by treatment with nimodipine.

Fibrinolysis↗
PubMed2001

Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review.

BACKGROUND AND PURPOSE: Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials. METHODS: - We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Embase. We assessed whether these studies showed a beneficial effect of active treatment. In-depth analyses were performed on infarct size and amount of edema, and subgroup analyses were performed on the length of the time window to the initiation of treatment and the methodological quality of the studies. RESULTS: - Of 225 identified articles, 20 studies were included. The methodological quality of the studies was poor. Of the included studies, 50% were in favor of nimodipine. In-depth analyses showed statistically significant effects in favor of treatment (10 studies). No influence of the length of time to the initiation of treatment or of the methodological quality on the results was found. CONCLUSIONS: - We conclude that the results of this review did not show convincing evidence to substantiate the decision to perform trials with nimodipine in large numbers of patients. There were no differences between the results of the animal experiments and clinical studies. Surprisingly, we found that animal experiments and clinical studies ran simultaneously.

Animals↗
PubMed2000

['Another breakthrough': general news reports raise false hopes].

Recently a breakthrough in research was reported in the Dutch press. The results were considered of major importance for the treatment of patients with Parkinson's disease, motor neuron disease and Alzheimer's disease. Thereafter societies of patients and neurologists were overloaded with questions. They had to explain again and again that false expectations had been aroused. The road from basic research to a proven beneficial therapy is long. Promising results are at many phases of the development of a treatment at risk of disappearing. Reports from the laboratory on new treatments are always too early. In order to prevent false expectations, submissions to the press ought to be based on firm evidence as is usual with publications in professional journals, editors of the press should scrutinize the claims made by researchers, and, in addition, the general public should be educated on the diagnostic process and the assessment of treatment efficacy.

Deception↗
PubMed2000

Multifocal inflammatory demyelinating neuropathy: a distinct clinical entity?

BACKGROUND: Several patients have been reported with an asymmetric sensory or sensorimotor demyelinating neuropathy not fulfilling the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy or multifocal motor neuropathy. OBJECTIVE: To present the clinical, electrophysiologic, radiologic, and pathologic features of six patients with an asymmetric sensory or sensorimotor demyelinating neuropathy. RESULTS: All six patients were initially affected in only one limb; in four patients the neuropathy progressed to other limbs in an asymmetric fashion during several years. On electrophysiologic examination, evidence of multifocal demyelination and conduction block in motor and sensory nerves was found in all patients. MRI of the brachial plexus revealed swollen nerves and an increased signal intensity on T2-weighted imaging in four patients. A biopsy sample taken from the brachial plexus of one patient revealed evidence of inflammation. All patients showed a beneficial response to IV immunoglobulin treatment. Thirty-four similar patients have been reported previously, many of whom were initially diagnosed as having various other (nontreatable) diseases. CONCLUSIONS: The authors propose calling this neuropathy "multifocal inflammatory demyelinating neuropathy" and considering it as a distinct clinical entity to facilitate early diagnosis of this treatable disorder.

Adult↗
PubMed2000

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rupture of an intracranial aneurysm causes bleeding into the subarachnoid space, which may lead to spasm of the cerebral arteries and ischaemic damage to the brain. Prophylactic use of calcium antagonists in patients with ruptured intracranial aneurysms might reduce the risk of ischaemic damage. OBJECTIVES: This review aimed to determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). SEARCH STRATEGY: The Cochrane Stroke Group trials register (last searched: March 1999) plus hand searching and personal contacts with trialists and pharmaceutical companies marketing calcium antagonists. SELECTION CRITERIA: All completed, unconfounded, truly randomised controlled trials comparing any calcium antagonist with control, within ten days of SAH onset. Eleven trials that met the inclusion criteria were included in the overview. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We analysed 11 trials totalling 2804 randomized patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analyzed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877 (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by angiography or autopsy. Overall, calcium antagonists significantly reduce the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0. 72-0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event is 20. For oral nimodipine alone the RR was 0.69 (0.58-0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80-1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59-0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71-0.89). REVIEWER'S CONCLUSIONS: Calcium antagonists reduce the proportion of patients with poor outcome and ischemic neurological deficits after aneurysmal SAH; the risk reduction for case fatality alone is not statistically significant. The results for 'poor outcome' are statistically robust, but depend mainly on trials with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH remain uncertain.

Calcium Channel Blockers↗
PubMed2000

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Re-bleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. This is probably due to dissolution of the clot by natural fibrinolytic activity. OBJECTIVES: The objective of this review was to assess the effect of antifibrinolytic treatment in patients with aneurysmal subarachnoid haemorrhage. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and reference lists of articles. We also contacted drug companies. SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid or an equivalent) with control in people with confirmed subarachnoid haemorrhage. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the data. All five reviewers assessed trial quality. MAIN RESULTS: Eight trials involving 937 patients were included. Based on 579 patients in two trials, antifibrinolytic treatment did not show any benefit for poor outcome (death, vegetative state or severe disability) with an odds ratio of 1.05, 95% confidence interval 0.76 to 1.46. Death from all causes was not significantly influenced by treatment across all eight trials (odds ratio 0.96, 95% confidence interval 0.72 to 1.26). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up, with some heterogeneity between the trials (odds ratio 0.59, 95% confidence interval 0.42 to 0.81). Treatment increased the risk of cerebral ischaemia in four trials (odds ratio 2.03, 95% confidence interval 1.40 to 2.94). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in four trials (odds ratio 1. 05, 95% confidence interval 0.71 to 1.56). REVIEWER'S CONCLUSIONS: Antifibrinolytic treatment does not appear to benefit people with aneurysmal subarachnoid haemorrhage. However, the trials were all done more than 10 years ago. New strategies may counteract the ischaemia-inducing potential of antifibrinolytic treatment and lead to improved outcome. A trial of combined antifibrinolytic and anti-ischaemia treatment is underway.

Antifibrinolytic Agents↗
PubMed2000

Gender differences in job strain, social support at work, and psychological distress.

Using the demand-control-support model of job strain, the authors examined gender differences in the relationship between psychosocial work exposures and psychological distress in a cross-sectional sample of 7,484 employed Canadians. Compared with low-strain work, high-strain and active work were associated with a significantly higher level of distress in both men and women. Differences in psychological distress in relation to psychosocial work exposures were greater for men than for women. Low social support was associated with higher distress across all categories of job strain, and the combined effect of low social support and high job strain was associated with the greatest increase in distress. This pattern was similar in men and women. This study suggests that psychosocial work exposures may be a more significant determinant of psychological well-being in male workers compared with female workers.

Adult↗