Biomedical subjects

P J Jongen

Publications and source records attributed to P J Jongen.

At least 19 recordsLinked to original sources

PubMed2001

Hypointense lesions on T1-weighted spin-echo magnetic resonance imaging: relation to clinical characteristics in subgroups of patients with multiple sclerosis.

CONTEXT: Hypointense lesions on T1-weighted spin-echo magnetic resonance images (T1 lesions) represent destructive multiple sclerosis (MS) lesions, consisting of axonal loss and matrix destruction. These lesions are being used as a secondary outcome measure in phase III clinical trials. Clinical determinants of T1 lesions may differ between subgroups of patients with MS and subsequently may have implications for the selection of patients for clinical trials. OBJECTIVE: To determine if clinical characteristics of patients with MS are related to T1 lesion volume. DESIGN: A survey of 138 patients with MS (52 with relapsing-remitting MS, 44 with secondary progressive MS, and 42 with primary progressive MS). SETTING: The Magnetic Resonance Center for Multiple Sclerosis Research, University Hospital "Vrije Universiteit," Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: Type of MS, Expanded Disability Status Scale (EDSS) score, sex, age at first symptoms, and T1 lesion volume. RESULTS: Patients with secondary progressive MS have the highest T1 lesion volume. Patients with relapsing-remitting MS have a lower T1/T2 ratio than patients with secondary progressive MS and patients with primary progressive MS. In patients with relapsing-remitting MS and secondary progressive MS, T1 lesion volume relates to disease duration and EDSS score, while in patients with primary progressive MS sex is important. A trend toward higher T1 lesion volume was shown for male patients with primary progressive MS when compared with female patients with primary progressive MS (1.0 cm(3) vs 0.3 cm(3), P=.03); a trend toward higher T1 lesion volume was found with age at onset in patients with relapsing-remitting MS and in patients with primary progressive MS. CONCLUSIONS: In patients with MS different clinical characteristics associate with T1 lesion volume, suggesting a more destructive type of lesions in certain subgroups. A possible sex difference in (destructive) lesion development on magnetic resonance imaging should be evaluated in more detail, preferably in a cohort.

Adult↗

PubMed2001

Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis.

The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS and control subjects with respect to the percentage of maximal muscle force that could be recruited during voluntary effort (95.5 +/- 3.9% and 98.2 +/- 2.0%, respectively, P = 0.10), the stimulation frequency/force and force/velocity relationships, the rates of force development and relaxation, fatigue resistance, and the recovery rate of adductor pollicis muscle. However, previous results from the same group of MS patients showed that quadriceps femoris muscle force and resistance to fatigue were reduced. Therefore, our data support the clinical experience that, in patients with MS, lower limb muscle function is more or earlier affected than upper limb muscle function.

Adult↗

PubMed2001

Beyond unfavorable thinking: the illness cognition questionnaire for chronic diseases.

The literature on chronic diseases recognizes the role of illness cognition as a mediator between stress and illness. Few conceptualizations and instruments, however, give an indication of both unfavorable and favorable ways of adjusting to an uncontrollable long-term stressor, such as a chronic disease. The authors propose 3 generic illness cognitions that reflect different ways of reevaluating the inherently aversive character of a chronic condition: helplessness as a way of emphasizing the aversive meaning of the disease, acceptance as a way to diminish the aversive meaning, and perceived benefits as a way of adding a positive meaning to the disease. A self-report instrument, the Illness Cognition Questionnaire, was developed to assess these cognitions across different chronic diseases. The results support the reliable and valid assessment of these illness cognitions in patients with rheumatoid arthritis and multiple sclerosis and indicate the maladaptive function of helplessness and the adaptive function of acceptance and perceived benefits for the long-term physical and psychological health of patients with a chronic disease.

Adolescent↗

PubMed2000

Contractile properties and fatigue of quadriceps muscles in multiple sclerosis.

Functional characteristics of electrically stimulated quadriceps muscles of patients with multiple sclerosis (MS) were determined to investigate whether adaptations in muscle properties contribute to the higher fatigability of these patients. The estimated maximal isometric force generating capacity of MS patients was only 11.2% (P < 0.05) lower than control subjects. However, the patients were only able to voluntarily exert 75 +/- 22% (n = 12) of their maximal capacity, against 94 +/- 6% (n = 7) for the control subjects. There were no differences in muscle speed, suggesting that muscle fiber distribution was not different in the MS patients due to reduced muscle usage. During a series of repeated contractions, greater decrements occurred in isometric force and in maximal rate of force rise in the MS patients (by 31.3 +/- 10.3% and 50.1 +/- 10.0%, respectively; n = 13) than control subjects (23.8 +/- 6.6% and 39.0 +/- 8.1%, n = 15), suggesting a lower oxidative capacity. The results indicate that increasing the mass of their muscles by training may help to reduce the excessive muscle fatigue of MS patients.

Adult↗

PubMed2000

Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system.

OBJECTIVES: Validation of cerebrospinal fluid (CSF) indexes as a measure for intrathecal C3 and C4 production. Examination of their role in differential diagnosis of immunological disorders of the central nervous system (CNS). MATERIAL AND METHODS: Correlative study in controls (low back pain without disk herniation) between the CSF/serum ratio (Q) for albumin, and Q C3 and Q C4. Comparative study of C3 and C4 indexes in patients with CNS dysfunction due to relapsing-remitting (RR) multiple sclerosis (MS), secondary progressive (SP) MS, systemic lupus erythematosus (SLE), and human immunodeficiency virus (HIV) infection. RESULTS: Strong and statistically highly significant correlations between Q albumin and Q C3 (r=0.89, P=0.0001), and Q C4 (r=0.68, P= 0.0001). In MS patients decreased mean values for serum (RR, SP) and CSF (RR) C3, and increased C3 index mean value (RR, SP). In CNS SLE increase of mean C3 and C4 index values. In CNS HIV increase of mean C3 and C4 index values, and CSF C3 and C4 concentrations. Most individual index values were within the reference range. CONCLUSION: CSF index is a valid tool to detect intrathecal C3 or C4 production. C3 or C4 index contributes little to the differential diagnosis of immunological CNS disorders. C3 might play a pathogenic role in various immunological CNS disorders.

AIDS Dementia Complex↗

PubMed2000

Abnormal neuropsychological findings are not necessarily a sign of cerebral impairment: a matched comparison between chronic fatigue syndrome and multiple sclerosis.

OBJECTIVE: The aim of this study was to assess the potential impact of effort in comparative studies assessing neurocognitive dysfunction in patients with and without a neurologic diagnosis. BACKGROUND: It was hypothesized that a subgroup within a group of patients with prominent neurocognitive complaints but without a neurologic diagnosis would have impaired performance on a task originally designed to detect malingering. METHOD: We compared the neuropsychological performance of a group of 40 patients with a definite diagnosis of multiple sclerosis (MS) with that of 67 patients with chronic fatigue syndrome (CFS). The Amsterdam Short-Term Memory Test, a forced-choice memory task, served as measure to detect submaximal effort. In addition, we administered a regular neuropsychological task generally considered to be sensitive for cognitive deterioration. RESULTS: Compared with the MS group (13%), a larger proportion of the matched CFS group (30%) obtained scores indicative of reduced effort. In contrast, the proportions of patients scoring below the cutoff value on a conventional neuropsychological test did not differ significantly (17% of MS patients and 16% of CFS patients). CONCLUSIONS: The results obtained raise the question of to what extent abnormal test findings in the absence of documented neurologic impairment should be interpreted as a sign of cerebral impairment. The suggestion has been made to screen more often for biased results in comparative research studies so as to enhance valid interpretation of neuropsychological findings.

Adult↗

PubMed1999

High-performance liquid chromatography analysis, preliminary pharmacokinetics, metabolism and renal excretion of methylprednisolone with its C6 and C20 hydroxy metabolites in multiple sclerosis patients receiving high-dose pulse therapy.

A gradient eluent HPLC analysis in human plasma and urine was developed and validated for methylprednisolone (MP), its prodrug methylprednisolone-21-hemisuccinate (MPS) with the metabolites 6beta-hydroxy-6alpha-methylprednisolone (MPA), 20-hydroxymethylprednisolone (MPC), 6beta-hydroxy-20alpha-hydroxymethylprednisolone (MPB), 6beta-hydroxy-20beta-hydroxymethylprednisolone (MPE), 20-carboxymethylprednisolone (MPD), methylprednisolone-glucuronide (MPF) and 21-carboxymethylprednisolone (MPX). The column was Cp Spherisorb C8 5 microm, 250 mm x 4.6 mm I.D. (Chrompack, Bergen op Zoom, The Netherlands) with a guard column 75 mm x 2.1 mm, packed with pellicular reversed-phase. The eluent was a mixture of acetonitrile and 0.067 M KH2PO4 buffer, pH 4.5. At t=O, the eluent consisted of 2% acetonitrile and 98% buffer (v/v). Over the following 35 min the eluent changed linearly until it attained a composition of 50% acetonitrile and 50% buffer (v/v). At 37 min (t=37) the eluent was changed over 5 min to the initial composition, followed by equilibration over 3 min. The flow-rate was 1.5 ml/min and UV detection was achieved at 248 nm. Preliminary pharmacokinetic data were obtained from one patient who showed illustrative plasma concentration-time curves and renal excretion-time profiles after a short-lasting infusion (0.5 h) of 1 g of methylprednisolone hemisuccinate. The half-life of prodrug methylprednisolone-21-hemisuccinate (MPS) was 0.3 h, that of metabolite MPX (21-carboxy MP) was 0.4 h and that of the parent drug methylprednisolone (MP) was 1.4 h. The half-lives of the metabolites are almost similar (4 h). The main compounds in the urine are methylprednisolone hemisuccinate (prodrug, 15.0%), methylprednisolone (parent drug, 14.6%), metabolite MPD (20-carboxy, 11.7%), and metabolite MPB (13.2%). The renal clearance values of metabolites MPB, MPC and MPD are approximately 500 ml/min, that of MP is 100 ml/min.

Anti-Inflammatory Agents↗

PubMed1999

Isolation and identification of the C6-hydroxy and C20-hydroxy metabolites and glucuronide conjugate of methylprednisolone by preparative high-performance liquid chromatography from urine of patients receiving high-dose pulse therapy.

In the present study metabolites of methylprednisolone were detected using gradient elution high-performance liquid chromatography. Separation was performed by a Cp Spherisorb ODS 5 microm (250 mmx4.6 mm I.D.) column, connected to a guard column, packed with pellicular reversed phase. The mobile phase was a mixture of acetonitrile and 1% acetic acid in water. At t = 0, this phase consisted of 2% acetonitrile and 98% acetic acid 1% in water (v/v). During the following 35 min the phase changed linearly until it attained a composition of acetonitrile-buffer (50:50, v/v). At 40 min (t = 40) the mobile phase was changed over 5 min to the initial composition, followed by equilibration during 2 min. The flow-rate was 1.5 ml/min. UV detection was achieved at 248 nm. We have isolated the respective compounds with the most abundant concentration and suggested their chemical structure based on NMR, IR, UV, MS, retention behaviour and melting points. The c/, stereochemistry could not be solved in this study. The overall picture of the metabolic pathways of methylprednisolone is apparently simple: reduction of the C20 carbonyl group and further oxidation of the C20-C21 side chain (into C21-COOH and C20-COOH), in competition with or additional to the oxidation at the C6-position.

Chromatography, High Pressure Liquid↗

PubMed1999

High-performance liquid-chromatographic-atmospheric-pressure chemical-ionization ion-trap mass-spectrometric identification of isomeric C6-hydroxy and C20-hydroxy metabolites of methylprednisolone in the urine of patients receiving high-dose pulse therapy.

Fourteen metabolites of methylprednisolone have been analysed by gradient-elution high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The compounds were separated on a Cp Spherisorb 5 microm ODS column connected to a guard column packed with pellicular reversed phase. The mobile phase was an acetonitrile- 1.0% aqueous acetic acid gradient at a flow rate of 1.5 mL min(-1) The analysis gave a complete picture of parent drug, prodrugs and metabolites, and the alpha/beta stereochemistry was resolved. The short (1-2 h) elimination half-life of methylprednisolone is explained by extensive metabolism. The overall picture of the metabolic pathways of methylprednisolone is apparently simple-reduction of the C20 carbonyl group and further oxidation of the C20,C21 side chain (into C21COOH and C20COOH), in competition with or in addition to oxidation at the C6 position.

Anti-Inflammatory Agents↗

PubMed1998

Fatigue in multiple sclerosis: interrelations between fatigue complaints, cerebral MRI abnormalities and neurological disability.

Although fatigue is a frequent complaint of patients with multiple sclerosis (MS), little is known about the origins of multiple-sclerosis-associated fatigue. Our primary focus was to study if the extent of cerebral abnormalities, as shown on magnetic resonance imaging (MRI), had any relation with the frequency and intensity of fatigue complaints of patients with a definite diagnosis of MS. Fatigue severity was rated by the patients with the use of a 2-week diary and a fatigue questionnaire, while conventional T1- and T2-weighted MRI provided several measures for cerebral abnormalities. In total, 72% of 45 patients reported to be seriously fatigued at least several times a week over the last 3-month period. Fatigue severity was not related to the total extent of cerebral abnormalities, or to MRI-based atrophy measures. Regional lesion load did not differ between fatigued and non-fatigued subjects. Although neurological disability, as measured by the Expanded Disability Status Scale (EDSS) and Neurological Rating Scale (NRS), did correlate significantly with most MRI measures, it showed no relation with fatigue severity. Neurological progression rates and number of exacerbations in the 2-year period prior to assessment were not significantly associated with the fatigue measures. Therefore, our findings suggest that differences in levels of self-reported fatigue in patients with multiple sclerosis cannot merely be explained by the degree of clinical disease activity, neurological disability or the extent of MRI abnormalities. These results are compared to other research findings and the possible role of alternative factors influencing fatigue in multiple sclerosis are discussed.

Adult↗

PubMed1998

The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model.

The cause of chronic fatigue syndrome (CFS) is unknown. With respect to factors perpetuating fatigue, on the other hand, a model has been postulated in the literature in which behavioral, cognitive, and affective factors play a role in perpetuating fatigue. In the present study, this hypothesized model was tested on patients with CFS and on fatigued patients with multiple sclerosis (MS). The model was formulated in terms of cause-and-effect relationships and an integral test of this model was performed by the statistical technique, "structural equation modeling," in 51 patients with chronic fatigue syndrome and 50 patients with multiple sclerosis matched for age, gender, and education. Attributing complaints to a somatic cause produced low levels of physical activity, which in turn had a causal effect on fatigue severity. Depression had to be deleted from the model. Sense of control over symptoms and focusing on bodily symptoms each had a direct causal effect on fatigue. The model showed an excellent fit for CFS patients, but was rejected for MS patients. Therefore, a new model for MS patients had to be developed in which sense of control had a causal effect on fatigue. In the MS model, no causal relationship was found between the physical state as measured by the Expanded Disability Status Score (EDSS) and fatigue or functional impairment. The present study shows that cognitive and behavioral factors are involved in the persistence of fatigue. Treatment should be directed at these factors. The processes involved in the subjective experience of fatigue in CFS were different from the processes related to fatigue in MS.

Adult↗

PubMed1998

A novel gamma-sarcoglycan mutation causing childhood onset, slowly progressive limb girdle muscular dystrophy.

Limb girdle muscular dystrophy is a heterogeneous group of disorders. One autosomal recessive subtype, LGMD2C, has been linked to chromosome 13, and is caused by gamma-sarcoglycan deficiency in muscle. This report describes a novel missense mutation identified in a large consanguineous Dutch family with LGMD. This mutation leads to reduction of gamma-sarcoglycan, and gives rise to a childhood-onset, slowly-progressive dystrophy.

Adolescent↗

PubMed1998

Sexual dysfunction in men with multiple sclerosis--a comprehensive pilot-study into etiology.

UNLABELLED: Ideally, the etiological diagnosis of sexual dysfunction in patients with multiple sclerosis is established on the basis of both objective and subjective tests. Accordingly, we assessed sexual function in 16 male patients with multiple sclerosis and complaints of sexual dysfunction by means of subjective data from interviews and questionnaires and objective data, obtained from (psycho)physiological tests. Psychophysiological investigation consisted of measurement of sleep erections and of erectile response to visual erotic stimulation and penile vibration. Urodynamic investigation was used to assess the neurological status of the genital tract. Sixteen male patients with clinically definite multiple sclerosis, complaints of sexual dysfunction and a steady heterosexual relationship participated in the study. The majority of patients had no abnormalities in the objective tests. Only one (1 out of 15) patient showed disturbed sleep-erections, and four (4 out of 12) other patients showed signs of neurological dysfunction of the genital tract. CONCLUSION: In our patient-group, disturbed sleep erections and abnormal findings on urodynamic investigation appeared unrelated to the complaint of erectile dysfunction. Sexual function was related to psychological factors, decreased general sensitivity, and motor impairment.

Adolescent↗

PubMed1998

Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms.

We investigated various magnetic resonance MRI parameters for both brain and spinal cord to see if any improved the clinicoradiological correlation in multiple sclerosis. Ninety-one multiple sclerosis patients (28 relapsing-remitting, 32 secondary progressive and 31 primary progressive) were imaged using conventional T1, proton density- and T2-weighted MRI of the brain and spinal cord. Focal brain and spinal cord lesion load was scored, as were diffuse signal abnormalities, brain ventricular volume and spinal cord cross-sectional area. Clinical measures included the expanded disability status scale (EDSS), the functional systems score and a dedicated urology complaint questionnaire. Secondary progressive patients differed from relapsing-remitting and primary progressive patients by a larger number of hypointense T1 lesions in the brain, ventricular enlargement and spinal cord atrophy. Primary progressive patients more often had diffuse abnormalities in the brain and/or spinal cord than did relapsing-remitting and secondary progressive patients. In the entire study population, EDSS correlated with both brain and spinal cord MRI parameters, which were independent. The urological complaint score correlated only with spinal cord MRI parameters. In relapsing-remitting and secondary progressive multiple sclerosis, the correlation between MRI and clinical parameters was better than in the entire population. In this subgroup EDSS variance could be explained best by T1 brain lesion load, ventricle volume and spinal cord cross-sectional area. In the primary progressive subgroup the clinicoradiological correlation was weak for brain parameters but was present between spinal cord symptoms and spinal cord MRI parameters. In conclusion, the different brain and spinal cord MRI parameters currently available revealed considerable heterogeneity between clinical subtypes of multiple sclerosis. In relapsing-remitting and secondary progressive multiple sclerosis both brain and spinal cord MRI may provide a tool for monitoring patients, while in primary progressive multiple sclerosis the clinicoradiological correlation is weak for brain imaging.

Adult↗

PubMed1998

Hereditary neuropathy with liability to pressure palsies. Phenotypic differences between patients with the common deletion and a PMP22 frame shift mutation.

In six families with hereditary neuropathy with liability to pressure palsies (HNPP) the 17p11.2 deletion was absent, but single strand conformation-analysis and subsequent sequencing demonstrated a heterozygous G-insertion in a stretch of six Gs at nt 276281 of the PMP22 gene, resulting in a frame shift after Gly94. Haplotype comparison of the six families revealed common ancestry. We compared the phenotype of 23 patients from these six families with the phenotype of 63 patients of 17 families with the common deletion. The patients with the G-insertion showed the clinical, electrophysiological and morphological characteristics of common HNPP, but in addition they had significantly more neuropathic features, mimicking hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1). To explain this distinct phenotype we suggest that, by translation of the mutated gene, a markedly changed polypeptide is formed without the normal cytoplasmic C-terminal of the native protein, resulting in a loss of function similar to that with the common deletion, but exerting an extra disturbance of Schwann cell functions, probably by hampering normal myelin formation or maintenance.

Adolescent↗

PubMed1998

The heart in limb girdle muscular dystrophy.

OBJECTIVE: To assess the frequency, nature, and severity of cardiac abnormalities in limb girdle muscular dystrophy, and its relation to age and weakness in various genotypes. DESIGN: In 26 autosomal dominant, 38 autosomal recessive, and 33 sporadic strictly defined patients with limb girdle muscular dystrophy, cardiac evaluation included history, physical examination, chest x ray, electrocardiography, 24 hour ECG Holter monitoring, and echocardiography. In 35 of the 71 autosomal recessive and sporadic cases muscle biopsies were available for sarcoglycan analysis. MAIN RESULTS: Dilated cardiomyopathy was present in one autosomal dominant case and in three advanced autosomal recessive or sporadic patients, of whom two were found to have alpha sarcoglycan deficiency. Two of these three patients and three other cases showed ECG abnormalities known to be characteristic of the dystrophinopathies. A strong association between the absence of alpha sarcoglycan and the presence of dilated cardiomyopathy was found (p = 0.04). In six autosomal dominant cases there were atrioventricular (AV) conduction disturbances, increasing in severity with age and in concomitant presence of muscle weakness. Pacemaker implantation was necessary in four. CONCLUSIONS: 10% of these patients had clinically relevant cardiac abnormalities. In autosomal dominant limb girdle muscular dystrophy one subtype characterised by muscle weakness and AV conduction disturbances is recognised. In the course of autosomal recessive/sporadic limb girdle muscular dystrophy, dilated cardiomyopathy may develop, probably related to deficiency of dystrophin associated proteins.

Adolescent↗

PubMed1998

Composite cerebrospinal fluid score in relapsing-remitting and secondary progressive multiple sclerosis.

We investigated whether cerebrospinal fluid (CSF) analysis may differentiate between relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). In 17 RR and 16 SP patients we determined: albumine CSF/PB ratio; mononuclear cell (MNC) number, CD4+, CD8+, and B1+ subsets, CD4+/CD8+ ratio; IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indexes; myelin basic protein; neuron-specific enolase (NSE); S100; and lactate. For each parameter the statistical distance was calculated. Then, using linear discriminant analysis, we computed a discriminant score, including only variables with a P value less than or equal to 0.15: albumin CSF/PB ratio, MNC number, IgM, IgM index, C3, C4, NSE, S100, and lactate. The discriminant score allocated all 17 RR patients to the RR group and 15 of 16 SP patients to the SP group. We conclude that RR and SP MS patients differ with respect to CSF profile and that in individual patients a composite CSF score may differentiate between RR and SP MS.

Adult↗

PubMed1998

Myelin basic protein in CSF as indicator of disease activity in multiple sclerosis.

There is an evident need for a quantitative laboratory marker for ascertaining disease activity and treatment effects in multiple sclerosis (MS) patients. Activity of the disease process in MS is accompanied by myelin breakdown and appearance of myelin basic protein (MBP) in cerebrospinal fluid (CSF). In this paper MBP in CSF of relapsing-remitting (RR) MS patients is reviewed. MBP in CSF is a fragment containing an epitope corresponding to amino acid residues 45-89 of the native molecule. From several relevant studies about CSF MBP in RR MS the following relations can be concluded: CSF MBP levels in active MS patients are frequently increased (45-100%), remain increased until 5 to 6 weeks after onset symptoms and are higher in polysymptomatic exacerbations and correlate with number of gadolinium-enhanced (Gd) lesions on MRI, severity of relapses, EDSS score and CSF intrathecal IgM synthesis. After an intravenous methylprednisolone treatment the increased CSF MBP levels return to normal values and reduction in CSF MBP is related to reduction in EDSS score, number of Gd lesions and CSF intrathecal IgM synthesis.

Epitopes↗