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Biomedical subjects

M Vermeulen

Publications and source records attributed to M Vermeulen.

At least 91 records · Page 5Linked to original sources

Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND AND PURPOSE: It has been reported that nimodipine reduces the frequency of secondary ischemia and improves outcome after aneurysmal SAH, but definitive evidence concerning all available calcium antagonists is lacking. METHODS: Systematic overview of randomized trials that were completed by January 1996 compared calcium antagonists with control and started treatment within 10 days after onset of subarachnoid hemorrhage (SAH) was performed. All calcium antagonists studied thus far (nimodipine, nicardipine, and AT877) were included. RESULTS: We analyzed 10 trials totaling 2756 patients. The relative risk (RR) reduction of poor outcome (death or dependency) was 16% (95% CI, 6 to 27%) and that of case fatality was 10% (95% CI, -6 to 25%). To prevent one poor outcome, 19 (12 to 59) patients need to be treated. Calcium antagonists give a 33% (95%, CI 25 to 41) RR reduction in the frequency of ischemic neurologic deficit and a 20% (95% CI, 11 to 28) RR reduction in the frequency of CT-scan documented cerebral infarction. Eight (6 to 11) patients need to be treated to prevent one ischemic neurologic deficit. In the analyses for nimodipine only, treatment was associated with a 24% RR reduction of poor outcome (95% CI, 12 to 38). To prevent one poor outcome, 13 (8 to 30) patients need to be treated with nimodipine. The RR reduction of angiographically detected cerebral vasospasm was statistically significant for AT877 (38%; 95% CI, 17 to 54%) and nicardipine (21%; 95% CI, 6 to 34%) but not for nimodipine (9%; 95% CI, -2 to 19%). CONCLUSION: Calcium antagonists reduce the proportion of ischemic neurologic deficits and nimodipine improves overall outcome within 3 months of aneurysmal SAH; evidence for a reduction of poor outcome from all causes by nicardipine and AT877 is inconclusive. The intermediate factors by which nimodipine exerts its beneficial effect remain uncertain.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Pulsed high dose dexamethasone treatment in chronic inflammatory demyelinating polyneuropathy: a pilot study.

Six cycles of dexamethasone (40 mg per day for four sequential days) every 28 days induced remissions in 10 patients with idiopathic thrombocytopenic purpura (ITP). Whether the same results could be achieved in 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was investigated by comparing the Rivermead mobility index (RMI) before and after six cycles of treatment. Three patients discontinued treatment: one because of severe nausea and vomiting and two because of neurological deterioration. All seven patients who completed treatment improved on the RMI. One of these patients had a relapse within two months after the last cycle and six patients were in remission six months after the last dexamethasone cycle. Pulsed high dose dexamethasone induced remissions ranged from at least 15 to 23 months. This treatment needs to be tested against standard treatment in a randomised study.

Adult↗

Timing of surgery in patients with aneurysmal subarachnoid haemorrhage: rebleeding is still the major cause of poor outcome in neurosurgical units that aim at early surgery.

OBJECTIVE: To investigate prospectively the proportion of patients actually operated on early in units that aim at surgery in the acute phase of aneurysmal subarachnoid haemorrhage (SAH) and what is the main current determinant of poor outcome. METHODS: A prospective analysis of all SAH patients admitted during a one year period at three neurosurgical units that aim at early surgery. The following clinical details were recorded: age, sex, date of SAH, date of admission to the neurosurgical centre, whether a patient was referred by a regional hospital or a general practitioner, Glasgow coma scale and grade of SAH (World Federation of Neurological Surgeons (WFNS) score) on admission at the neurosurgical unit, results of CT and CSF examination, the presence of an aneurysm on angiography, details of treatment with nimodipine or antifibrinolytic agents, and the date of surgery to clip the aneurysm. At follow up at three months, the patients' clinical outcome was determined with the Glasgow outcome scale and in cases of poor outcome the cause for this was recorded. RESULTS: The proportion of patients that was operated on early--that is, within three days after SAH--was 55%. Thirty seven of all 102 admitted patients had a poor outcome. Rebleeding and the initial bleeding were the main causes of this in 35% and 32% respectively of all patients with poor outcome. CONCLUSIONS: In neurosurgical units with what has been termed "modern management" including early surgery, about half of the patients are operated on early. Rebleeding is still the major cause of poor outcome.

Adult↗

Machado-Joseph disease presenting as severe asymmetric proximal neuropathy.

Despite much effort, a 74 year old man with progressive proximal weakness and sensory disturbances due to axonal neuropathy remained a diagnostic problem. Investigation of his family disclosed an additional patient with a cerebellar syndrome and a family member with mainly pyramidal features. Analysis of DNA showed a CAG repeat expansion in the Machado-Joseph disease gene in all three patients. Although not conclusively proved, we think that the neuropathy of the index case is linked to the CAG repeat expansion. Machado-Joseph disease should be considered in progressive axonal neuropathy.

Adult↗

Immunomodulation and remyelination: two aspects of human polyclonal immunoglobulin treatment in immune mediated neuropathies?

Intravenous immunoglobulin is used in inflammatory demyelinating diseases of the peripheral as well as the central nervous system. It is not known which mechanism(s) accounts for the beneficial effect observed in these diseases. The immunomodulatory effects of IVIg in two different models of T and B cell activation were investigated. IVIg inhibited a predominantly cellular immune response of the Th 1 type, which was partially reversed by addition of Th 1 cytokines. In contrast, in a model, which leads to B cell differentiation and antibody production, a synergistic stimulatory effect of IVIg and Th2 cytokines was observed. The ability of IVIg to interfere with cell proliferation and to manipulate the Th1/Th2 profile will have consequences for the induction, character, and amplification of an immune response. Apart from the immunomodulatory effects, evidence shows that IVIg promote remyelination not only by abrogation of the auto-immune attack but also by an effect on glial cells. We showed that IVIg induce growth arrest of normal human fibroblasts and Schwann cells. In fibroblasts this growth arrest is accompanied by upregulation of GAS-3/PMP-22 mRNA. The implications of this finding are discussed. Further studies in human Schwann cells are imperative to prove the hypothesis that IVIg directly stimulates remyelination.

Autoimmune Diseases↗

Unusual recovery from acute panautonomic neuropathy after immunoglobulin therapy.

A 33-year-old woman with acute idiopathic postganglionic panautonomic neuropathy experienced prompt recovery of all dysautonomic symptoms after receiving high-dose intravenous immunoglobulin therapy. Her recovery was complete within 6 months after onset of disease. This unusually rapid and complete recovery in comparison with that of historical control subjects suggests that patients with acute, severe, and widespread autonomic failure might benefit from intravenous immunoglobulin therapy.

Acute Disease↗

Subarachnoid haemorrhage: diagnosis and treatment.

In this review the diagnosis and management of the acute phase of subarachnoid haemorrhage (SAH) are discussed. CT is a sensitive method of predicting a ruptured aneurysm in patients with SAH. If angiography does not reveal an aneurysm, the bleeding pattern on CT may predict if a patient is still at risk of rebleeding. Spectophotometric analysis of the CSF is a reliable method of distinguishing between traumatic tap and SAH and is a sensitive method of detecting SAH even 4 weeks after the bleeding. Many kinds of treatment can be considered in SAH, but few have been tested in well-conducted clinical trials. Based on the study methodology, different levels of evidence of treatment effectiveness can be distinguished. The effectiveness of nimodipine in reducing poor outcome has the most evidence in favour of it.

Humans↗

Nitric oxide synthase inhibitors enhance plasma levels of corticosterone and ACTH.

The role of nitric oxide in the regulation of adrenal steroidogenesis was examined in BALB/c mice by employing the nitric oxide synthase inhibitors NG-nitro L-arginine methyl ester (L-NAME) and NG-nitro L-arginine (L-NNA). The administration of a single dose of nitric oxide inhibitors (50 mg kg-1 body wt. i.p.) induced a fourfold increase in plasma corticosterone. Treatment with L-arginine (750 mg kg-1 body wt. s.c.), but not D-arginine, completely prevented corticosterone increases induced by L-NAME. To analyse whether the activation of adrenal steroidogenesis induced by nitric oxide synthase inhibitors involved the stimulation of the hypothalamo-pituitary-adrenal axis. ACTH levels were assessed. It was found that L-NAME significantly enhanced plasma ACTH concentrations. Genetic variations in this regulatory pathway are suggested by the fact that L-NAME increased corticosterone levels in BALB/c. C3H/He and DBA-2 mice, but not in C57BI/c mice, a strain characterized by a low steroid response to stress.

Adrenal Glands↗

Hyperphosphatasemia in early diagnosed infantile GM1 gangliosidosis presenting as transient hydrops fetalis.

The authors report a case of unsuspected fetal storage disorder initially diagnosed by placental examination performed because of a transient ascites at 28 weeks of gestation. At birth mild dysmorphic features and gradual neurological deterioration were observed. Highly elevated alkaline phosphatase levels were repeatedly noticed. Deficiency of beta-galactosidase was documented confirming GM1 gangliosidosis. Previous reports described the placental pathology after positive prenatal diagnoses of lysosomal diseases. In the present case, the postnatal diagnosis was made in view of the placental pathologic findings. Our observation indicates the need for thorough investigations in hydrops fetalis, in search for metabolic diseases.

Alkaline Phosphatase↗

Anti-beta-tubulin antibodies have no diagnostic value in patients with chronic inflammatory demyelinating polyneuropathy.

High-titre anti-beta-tubulin antibodies were recently reported to occur in over 50% of sera from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). It was concluded that these antibodies may help to distinguish CIDP from other neuropathies and that they are diagnostically useful. To verify these findings, we studied sera of 43 CIDP patients, only 3 of whom had anti-beta-tubulin antibodies. The differences between the results obtained cannot fully be explained by differences between patients or antigens but may be explained by the use of different techniques (Western blot versus ELISA). We used Western blot, which is less sensitive but far more specific, to detect these antibodies. The findings of our study did not confirm the high frequency of selective high-titre anti-beta-tubulin antibodies in CIDP patients. Therefore we conclude that binding to beta-tubulin by Western blot cannot serve as a marker of CIDP.

Adult↗

Differential effects of lignocaine and hypercalcaemia on anisotropic conduction and reentry in the ischaemically damaged canine ventricle.

OBJECTIVE: Anisotropic conduction characteristics, which may be expressed as the ratio of conduction velocities in the longitudinal (Vlong) and transverse (Vtrans) fibre directions, have been shown to stabilise reentry and favour the induction of sustained, uniform ventricular tachycardia. The aim of this study was to investigate whether interventions affecting either excitability (lignocaine) or both excitability and cell coupling (hypercalcaemia) might produce differential effects on the Vlong/Vtrans ratio, and whether an intervention reducing this ratio might prevent the induction of sustained reentrant ventricular tachycardia. METHODS: The effects of hypercalcaemia [8.2(SD 3.8) mmol.litre-1] and lignocaine infusion [to 24.4(19) and 42.3(29) mumol.litre-1] on Vlong and Vtrans were determined from 127 electrograms recorded with a plaque electrode on the anterior left ventricular wall of healthy dogs or 3 d after occlusion of the left anterior descending coronary artery. Vlong and Vtrans were computed from isochronal maps displaying ellipsoid patterns with a long axis corresponding to longitudinal conduction and a short axis corresponding to transverse conduction, as determined during basic (S1) and premature (S2) stimulation from the centre of the plaque electrode. Infarcted heart preparations were subjected to programmed stimulation for induction of reentrant ventricular tachycardias. RESULTS: Hypercalcaemia reduced both Vlong and Vtrans (P < 0.05) but did not modify either the Vlong/Vtrans ratio or the induction and patterns of ventricular tachycardias. Lignocaine reduced Vlong and the Vlong/Vtrans ratio during premature stimulation (S2) of infarcted heart preparations (P < 0.05) and stabilised reentrant ventricular tachycardias in preparations in which only nonsustained, multiform ventricular tachycardias were induced under control conditions. CONCLUSIONS: Conduction velocities in the longitudinal and transverse directions can be differentially affected by selected pharmacological interventions, but the Vlong/Vtrans ratio is not a representative index of the facilitating influence of tissue anisotropy on reentry. Therefore, the role of anisotropy in this model of reentry is not confined to establishing disparity of a functional character between conduction velocities in the longitudinal and transverse directions.

Animals↗

Outcome in patients with large intraventricular haemorrhages: a volumetric study.

Patients with large amounts of intraventricular blood have a poor prognosis. The question is whether the quantity of ventricular blood or other factors related to the origin of the intraventricular bleeding cause poor outcome. The association between ventricular blood volume and outcome was analysed in patients with a primary intraventricular haemorrhage (PIVH) and in patients with an aneurysmal subarachnoid haemorrhage (SAH). The medical records of 24 patients with PIVH were reviewed and these patients were compared with 59 patients selected from a prospectively studied series of patients with aneurysmal SAH who had intraventricular blood without an intraparenchymal haematoma. Glasgow coma score on admission and outcome at three months expressed on the Glasgow outcome scale were available for all patients. Volumetric analysis on CT was carried out if there was at least a moderate amount of blood measured with a semi-quantitative scale (SAH n = 30, PIVH n = 22). In patients with SAH more than 20 ml intraventricular blood was lethal, as previously shown for patients with intraparenchymal haemorrhage. Patients with a PIVH can, however, survive such large volumes of intraventricular blood without impaired consciousness immediately after the bleeding, without developing hydrocephalus, and without any disability after three months. It is concluded that the cause of an intraventricular haemorrhage is more important for outcome than the amount of intraventricular blood, and large intraventricular haemorrhages are not always associated with hydrocephalus.

Adolescent↗

Impairment, disability, or handicap in peripheral neuropathy: analysis of the use of outcome measures in clinical trials in patients with peripheral neuropathies.

Outcome measures can be classified into measures of impairment, disability, and handicap. To investigate the biological effect of treatment, measures of impairment are appropriate. Studies investigating whether patients benefit from treatment in terms of improvement of functional health, however, require disability or handicap measures. In a review of the medical literature between 1978 and 1993, 73 controlled intervention studies in patients with peripheral neuropathies were found. Disability or handicap measures were used in two of 54 studies in patients with diabetic neuropathy, in two of six studies in patients with chronic inflammatory demyelinating polyneuropathy, in none of five studies in a mixed group of patients, and in all eight studies in patients with Guillain-Barré syndrome. The limited use of disability and handicap measures in patients with diabetic and mixed neuropathies can be explained by the experimental nature of most studies. In four of six studies, however, in patients with chronic inflammatory demyelinating polyneuropathy or neuropathy associated with monoclonal gammopathy that were designed to assess effectiveness of treatment, the choice of outcome measures was not appropriate. It is concluded that in the design of intervention studies in patients with peripheral neuropathy more attention should be paid to a proper choice of suitable outcome measures to assess the effectiveness of treatment.

Activities of Daily Living↗