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Biomedical subjects

O R Hommes

Publications and source records attributed to O R Hommes.

At least 55 records · Page 3Linked to original sources
PubMed1992

The effects of high-dose methylprednisolone on gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid measurements in multiple sclerosis.

Blood-brain barrier (BBB) disruption is probably the first event in the lesion development in multiple sclerosis (MS). This stage can be visualized by gadolinium-enhanced magnetic resonance (MR) imaging of the brain. Serial MR imaging studies have indicated a continuous spectrum of disease activity with waxing and waning of acute lesions, even in clinically stable MS patients. High-dose intravenous methylprednisolone (MP) has a beneficial clinical effect; reduces gadolinium enhancement, indicating improvement of BBB integrity; and, in MS patients, decreases intrathecal immunoglobulin synthesis with reduction of cerebrospinal fluid (CSF) myelin basic protein (MBP). A correlative triad is noted between gadolinium enhancement, clinical improvement, and decrease of CSF MBP following MP treatment, indicating a relationship between restoration of BBB integrity, clinical improvement and decrease of myelin breakdown. It is not clear whether MP interferes primarily with the process of demyelination or reacts non-specifically with its mediators.

Gadolinium↗
PubMed1992

CSF myelin basic protein, IgG and IgM levels in 101 MS patients before and after treatment with high-dose intravenous methylprednisolone.

A total of 101 patients (62 women; 39 men) with definite MS were treated with 1000 mg methylprednisolone (MP) intravenously for 10 consecutive days. Immediately before and after MP treatment clinical scoring (Kurtzke's Expanded Disability Status Scale) and CSF analysis were performed. Before MP treatment CSF MBP, IgG and IgM immunoglobulin levels (CSF Ig, index and intrathecal synthesis) were significantly elevated. The mean CSF MBP levels were significantly higher in the relapsing-remitting (RR) and chronic progressive MS patients with relapses (CP + RR) than in the CP group without a RR disease course, respectively 2.1, 2.3 and 1.5 micrograms/l. A weak positive correlation was found between CSF MBP level and EDSS in the RR MS group (r = 0.34). CSF MBP was significantly correlated with IgM index (r = 0.36), IgM synthesis (r = 0.26), but not with the IgG levels. Therefore demyelination seems to be related to intrathecal IgM production. After MP treatment mean (median) EDSS decreased from 4.4 (4.0) to 3.3 (3.0). Except for Q albumin and IgM index, all CSF immunoglobulin levels decreased significantly after MP. The mean CSF MBP returned to reference values. In the RR group the decrease in CSF MBP was significantly correlated with the change in EDSS (r = 0.39). CSF MBP seems to be a good parameter for disease activity in relapsing MS. Following treatment CSF MBP was found to be related with the change in IgM index (r = 0.30). MP treatment reduces CSF MBP and intrathecal IgM in a similar way indicating a relation between these 2 parameters.

Adult↗
PubMed1992

EDMUS, a European database for multiple sclerosis.

EDMUS is a minimal descriptive record developed for research purposes to document clinical and laboratory data in patients with multiple sclerosis (MS). It has been designed by a committee of the European Concerted Action for MS, organised under the auspices of the Commission of the European Communities. The software is user-friendly and fast, with a minimal set of obligatory data. Priority has been given to analytical data and the system is capable of automatically generating data, such as diagnosis classification, using appropriate algorithms. This procedure saves time, ensures a uniform approach to individual cases and allows automatic updating of the classification whenever additional information becomes available. It is also compatible with future developments and requirements since new algorithms can be entered in the programme when necessary. This system is flexible and may be adapted to the users needs. It is run on Apple and IBM-PC personal microcomputers. Great care has been taken to preserve confidentiality of the data. It is anticipated that this "common" language will enable the collection of appropriate cases for specific purposes, including population-based studies of MS and will be particularly useful in projects where the collaboration of several centres is needed to recruit a critical number of patients.

Database Management Systems↗
PubMed1992

A correlative triad of gadolinium-DTPA MRI, EDSS, and CSF-MBP in relapsing multiple sclerosis patients treated with high-dose intravenous methylprednisolone.

In a prospective study, we compared the number of gadolinium-DTPA (Gd-DTPA) enhancing lesions on MRI with the CSF and clinical findings before and after a total of 20 courses of high-dose intravenous methylprednisolone in relapsing multiple sclerosis patients. Before treatment, there was a significant correlation of Gd-DTPA enhancement (seen on 16 of 20 scans) and CSF myelin basic protein (MBP). If enhancement with Gd-DTPA represents inflammation and CSF-MBP indicates myelin breakdown, the amount of inflamed tissue should correlate with the amount of myelin being damaged. Clinical improvement occurred following 15 of 20 courses, and decrease of Gd-DTPA enhancement in 12 of 16 scans; the mean CSF-MBP level was the only CSF variable to return to reference values. There was a significant correlative triad of decrease in CSF-MBP, Gd-DTPA enhancement, and clinical disability. Thus, the clinical effect of methylprednisolone might be accompanied by a reduction of inflammation and myelin breakdown.

Adult↗
PubMed1992

Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs clinical findings in determining disease activity.

OBJECTIVE: Sequential MR imaging frequently shows disease activity (clinically silent new brain lesions) in subgroups of patients with multiple sclerosis and therefore is valuable in monitoring the effects of treatment. Monitoring of disease activity in patients being treated for relapsing-remitting multiple sclerosis will increase in importance as new and safe therapies are developed. We studied sequential enhanced MR images of patients with early relapsing-remitting multiple sclerosis to define the MR features that indicate disease activity in this subgroup of patients and to compare MR imaging and clinical findings for this purpose. SUBJECTS AND METHODS: Seven patients with relapsing-remitting definite multiple sclerosis were examined monthly for 4-12 months. For each image, a standard repositioning protocol consisting of three images was used to ensure reproducibility of axial (double oblique) image planes, planned according to internal landmarks. A total of 58 unenhanced T2-weighted and enhanced T1-weighted MR images were obtained. RESULTS: MR images showed new enhancing lesions in six of the seven patients. On 25 (43%) of the 58 enhanced T1-weighted MR images, a total of 50 new enhancing lesions were observed, and on one image a reenhancing lesion was seen. The unenhanced T2-weighted images showed corresponding abnormalities for 92% of the new enhancing lesions. At follow-up, most lesions (86%) were enhanced on only one occasion: 4% were enhanced on more than two consecutive monthly MR examinations. Forty-nine percent of the lesions seen on T2-weighted images "disappeared" (beyond the resolution of the imaging system) after a mean follow-up of 3.5 months, especially lesions that were initially smaller than 5 mm. During the study, only five clinical relapses occurred in three patients (all at times when MR images showed contrast-enhancing lesions), and fixed disability did not increase. On 21 additional occasions, MR images showed new enhancing or reenhancing lesions in patients who were clinically stable at the time (4.2 times more clinically silent disease activity). CONCLUSION: Our results suggest that contrast-enhanced MR imaging is more sensitive than clinical monitoring for detecting new disease activity in patients with relapsing-remitting multiple sclerosis and that MR imaging might be useful in the evaluation of therapeutic regimens.

Adult↗
PubMed1991

Evidence for early lower urinary tract dysfunction in clinically silent multiple sclerosis.

The occurrence of micturition complaints as late sequelae of multiple sclerosis is well studied and documented. However, no reports exist on urologically asymptomatic patients with a relatively short disease duration. In a prospective study of 40 patients with definite multiple sclerosis (mean disease duration 5 years), urodynamic investigations (cystometry and pressure-flow study) were combined with neuro-urophysiological measurements (cortical evoked potentials and sacral reflex latencies). Patients with (13) and without (27) micturition complaints were investigated. Neurourodynamic abnormalities were seen in 35 of 40 patients (88%). The lower urinary tract proved to be afflicted by multiple sclerosis at an early stage of the disease. Early neurourodynamic investigations had clinical implications. All of the complaining and half of the noncomplaining patients showed urodynamic abnormalities upon which the need for further followup and eventual therapeutic intervention was based. We conclude that neurourodynamic testing of a urinary functional system can be worthwhile as part of the initial diagnostic evaluation in patients with proved multiple sclerosis.

Adult↗
PubMed1991

Recurrent prolonged coma due to basilar artery migraine. A case report.

A 25 year old patient presented with recurrent prolonged episodes of life-threatening coma varying from 3 to 10 days. The clinical recovery was slow. The history and technical examinations led to the diagnosis of basilar artery migraine (BAM). The etiology of the coma episodes is thought to be related to ischemic dysfunction of the rostral part of the brainstem due to severe spasm of the basilar artery demonstrated by arteriography. Exceptional are the recurrent prolonged coma episodes of sudden onset, the severe spasm of the basilar artery, and the suppression-burst and FIRDA pattern on the EEG examinations during the coma episodes.

Adult↗
PubMed1991

Quantitative MRI changes in gadolinium-DTPA enhancement after high-dose intravenous methylprednisolone in multiple sclerosis.

In 12 patients with definite multiple sclerosis who received a total of 21 courses of high-dose (1 gram daily for 10 consecutive days) intravenous methylprednisolone, we performed MRI of the brain with and without gadolinium-DTPA before and after treatment. On the initial MRI, there was a total of 98 enhancing lesions, 93 of which were also represented on the unenhanced images. After treatment, 13 patients improved clinically, and 78 of the lesions lost enhancement but remained visible on the unenhanced images. There were six new enhancing lesions on the second MRI. Thus, the blood-brain-barrier integrity improved after high-dose IV methylprednisolone, which correlated well with the clinical improvement. The lesions remaining visible on the unenhanced images indicate an incomplete histologic recovery at the time of the second scan, and also demonstrate that unenhanced MRI alone is not sufficient to monitor disease activity in the short term in multiple sclerosis.

Adult↗
PubMed1990

Folates: epileptogenic effects and enhancing effects on [3H]TBOB binding to the GABAA-receptor complex.

The biochemical mechanism responsible for the convulsive effects of folates was investigated. The epileptogenic effects of folates were determined in vivo by quantification of the seizures following intracortical application in rats. The rank order of epileptogenic effects is: folic acid greater than or equal to 5-HCO-H4 folate greater than H2 folate greater than 5-CH3-H4 folate. This sequence of epileptogenicity in vivo is compared to the rank order of the effects of folates on radioligand binding to the GABAA-receptor complex in vitro. The inhibitory potencies of folates on [3H]muscimol and [3H]diazepam bindings did not correlate with their epileptogenic effects. However, folates reverse the inhibiting effect of GABA on the binding of the cage convulsant [3H]TBOB [( 3H]t-butylbicycloorthobenzoate). The rank order of this in vitro effect (folic acid greater than 5-HCO-H4 folate greater than H2 folate = 5-CH3-H4 folate) resembles the rank order of epileptogenicity determined in vivo. A relationship between the in vivo and in vitro effects is therefore suggested.

Animals↗
PubMed1990

Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia.

Vitamin B12 and folate concentrations were measured in serum and cerebrospinal fluid (CSF) in 293 neurological patients. Serum and CSF vitamin B12 concentrations showed a positive correlation. In individual patients CSF B12 concentrations varied considerably for a given serum concentration. The median serum vitamin B12 concentration of the Alzheimer's type dementia group was significantly lower compared with that of a control group. Lower median CSF vitamin B12 concentrations were found in groups of patients with multiple sclerosis and Alzheimer's type dementia. Five patients with heterogeneous clinical pictures had unexplained low serum and CSF B12 concentrations without macrocytosis. Two patients had very high serum B12 and low-normal CSF concentrations which could be explained by a blood-brain barrier transport defect. Serum and CSF folate concentrations did not show significant differences between the various groups.

Adolescent↗
PubMed1989

Long-lasting effects of cyclophosphamide on lymphocytes in peripheral blood and spinal fluid.

Moderate doses of cyclophosphamide can cause effects on lymphocytes that may last for some time after discontinuation of the treatment. Since cyclophosphamide is also often used at high doses, we studied the short- and long-term effects of such a high dose (8 grams in 20 days) in 50 patients with chronic progressive multiple sclerosis with the use of monoclonal antibodies. The treatment caused a depletion of lymphocytes, especially CD4+ cells resulting in a significant decrease of the CD4/CD8 ratio. These changes can still be found up to 13.5 years after treatment. Although there was some recovery in the first few years after treatment this was only partial. Therefore, some of the effects of high dose cyclophosphamide on cellular immunity may be permanent. These changes should be taken into account when studying immune parameters or considering new treatments in these patients.

Adult↗
PubMed1988

The short-term effect of an immunosuppressive treatment on CSF myelin basic protein in chronic progressive multiple sclerosis.

CSF levels of myelin basic protein (MBP) and intrathecally produced CSF IgG (de novo IgG) were measured in 11 chronic progressive multiple sclerosis patients with a deteriorating course of the disease for at least 6 months preceding observation and a reference group of 17 neurological patients suffering from disc herniation. In the multiple sclerosis patients, CSF levels were determined just before and once in the period 3 to 10 weeks after the start of an immunosuppressive treatment with cyclophosphamide and prednisone. For multiple sclerosis patients the CSF MBP levels before treatment were significantly higher than for controls. The CSF MBP levels after the treatment were nearly all within the control range. The abnormal high concentration of intrathecally produced CSF IgG (de novo IgG) in multiple sclerosis patients was reduced after treatment. A correlation between CSF MBP and CSF de novo IgG in multiple sclerosis patients could not be demonstrated. If CSF MBP is an indicator of the (activity of) myelin breakdown in the brain, it can be concluded that an intensive immunosuppressive treatment in combination with prednisone has, at least, a short-term, beneficial effect on the amount of demyelinisation and possibly on the disease activity.

Adult↗
PubMed1987

Amenorrhea after immunosuppressive treatment of multiple sclerosis.

Interviews on changes in the menstrual cycle were taken from 38 women of fertile age, several years after immunosuppressive treatment (IS) with prednisone and cyclophosphamide (CP) for definite multiple sclerosis (MS). Serum FSH, LH and 17-beta-oestradiol levels were determined at the time of interview. MS in itself did not change the experience of menstrual cycles; 17 patients developed hypergonadotrophic amenorrhea during or after IS. Symptoms related to climacterium (c. q. flushing) were present in 15 of these patients. The onset of amenorrhea depended on the age at the time of IS and on the cumulative dose of CP. Older patients developed amenorrhea at a lower cumulative dose of CP than did younger patients. High estrogen oral contraceptives are advocated in oncology to prevent disturbance of ovarian function by anti-mitotic treatment. This policy is advisable in female MS patients treated with drugs like CP or azathioprine.

Adult↗
PubMed1985

Suppression of the development of experimental allergic encephalomyelitis by suramin.

Suramin was tested for its ability to suppress experimental allergic encephalomyelitis. Prophylactic administration caused significant reduction in the severity of the disease, incidence of paralysis and cellular infiltration in nervous tissue. Therapeutic treatment with suramin also caused a reduction in the severity of the disease, the incidence of paralysis and cellular infiltration, but to a lesser extent. Significantly fewer animals were paralysed for more than two days on therapeutic treatment.

Animals↗
PubMed1985

Modulation of experimental allergic encephalomyelitis in Lewis rats by monoclonal anti-T cell antibodies.

The effect of monoclonal antibodies to different T lymphocyte populations of the rat on the induction and the course of experimental allergic encephalomyelitis (EAE) was investigated. EAE was induced by injection of guinea pig spinal cord in adjuvant. Subcutaneous injections of monoclonal antibodies to all peripheral T lymphocytes (W3/13) abrogated or prevented the development of clinical EAE. Similar results were obtained in animals injected with monoclonal antibodies to T helper cells (W3/25) mixed with monoclonal antibodies to T nonhelper cells (OX8). Animals treated with either W3/25 or OX8 developed clinical EAE as the control rats (subcutaneous injected with normal mouse serum). Histological examination after the acute stage revealed no significant differences between rats treated prophylactically with W3/13, W3/25 or OX8 and rats injected with normal mouse serum. Animals treated prophylactically with a mixture of W3/25 and OX8 developed, on the whole, EAE with less histological severity compared to the control animals. Treatment of rats after the onset of the first clinical symptoms of EAE (tail flaccidity) with W3/13 resulted in a less fatal course of the disease. Compared to surviving rats injected with mouse serum (controls) the number of infiltrates were reduced in these rats treated therapeutically.

Animals↗
PubMed1985

The effect of myelin basic protein on the protease inhibitors alpha 1 antitrypsin and alpha 2 macroglobulin.

The effect of myelin basic protein (MBP) of central nervous tissue on the protease inhibitors, alpha 1 antitrypsin (a1AT) and alpha 2 macroglobulin (a2M) was studied in vitro. For this purpose, 2 characteristics of the protease inhibitors were used, viz. their pattern after isoelectric focusing and their trypsin-binding capacity. Both features of purified a2AT disappeared in the presence of MBP. The tests with a2M revealed that the formation and stability of the complex between a2M and protease were reduced. The results of this study suggest that MBP causes an increase in proteolytic activity by inactivating protease inhibitors. The potential relevance of these results for demyelinating processes in man and animal is discussed.

Animals↗
PubMed1984

The significance of total creatine kinase activity and isozyme determinations in cerebrospinal fluid of neurological patients.

Total CK activity is often increased in cerebrospinal fluid samples in neurological diseases (35%). These increased levels are frequently caused by CK M-chain activity and appear to have no diagnostic relevance. Furthermore, an obvious concentration gradient for total CK activity was often observed in two subsequent tubes from the same lumbar puncture. In this study, CK non-M activity is measured, being the sum of all CK activity not caused by the M-chain. A bioluminescence technique using anti-M-inhibiting antibodies was used for this purpose. In two subsequent tubes from the same lumbar puncture a difference of 8% in CK non-M activity was found. A similar gradient could be observed for total protein. Retrospectively, the correlation between CK non-M levels and the amount of brain tissue damage was studied in 81 neurological patients and in 19 healthy subjects. There was an obvious relation between the extent of brain tissue damage and the CSF CK non-M levels. The clinical results in this study are promising and justify a prospective study of the diagnostic relevance of this parameter in CSF in various patient groups.

Brain Diseases↗