Biomedical subjects
Publications and source records attributed to M de Visser.
We report a 32-year-old patient with Charcot-Marie-Tooth (CMT2B) including foot ulcerations. Genetic analysis identified a de novo mutation in the small GTP-ase late endosomal RAB7 gene, consisting of a c.471G>C, p.Lys157Asn missense mutation. This observation strongly supports the hypothesis that RAB7 mutations are responsible for CMT2B.
BACKGROUND: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. AIM: To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. METHODS: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. RESULTS: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). CONCLUSIONS: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.
Post-polio syndrome (PPS) is characterized by new or increased muscular weakness, atrophy, muscle pain and fatigue several years after acute polio. The aim of the article is to prepare diagnostic criteria for PPS, and to evaluate the existing evidence for therapeutic interventions. The Medline, EMBASE and ISI databases were searched. Consensus in the group was reached after discussion by e-mail. We recommend Halstead's definition of PPS from 1991 as diagnostic criteria. Supervised, aerobic muscular training, both isokinetic and isometric, is a safe and effective way to prevent further decline for patients with moderate weakness (Level B). Muscular training can also improve muscular fatigue, muscle weakness and pain. Training in a warm climate and non-swimming water exercises are particularly useful (Level B). Respiratory muscle training can improve pulmonary function. Recognition of respiratory impairment and early introduction of non-invasive ventilatory aids prevent or delay further respiratory decline and the need for invasive respiratory aid (Level C). Group training, regular follow-up and patient education are useful for the patients' mental status and well-being. Weight loss, adjustment and introduction of properly fitted assistive devices should be considered (good practice points). A small number of controlled studies of potential-specific treatments for PPS have been completed, but no definitive therapeutic effect has been reported for the agents evaluated (pyridostigmine, corticosteroids, amantadine). Future randomized trials should particularly address the treatment of pain, which is commonly reported by PPS patients. There is also a need for studies evaluating the long-term effects of muscular training.
A late onset axonal Charcot-Marie-Tooth phenotype is described, resulting from a novel mutation in the myelin protein zero (MPZ) gene. Comparative computer modelling of the three dimensional structure of the MPZ protein predicts that this mutation does not cause a significant structural change. The primary axonal disease process in these patients points to a function of MPZ in maintenance of the myelinated axons, apart from securing stability of the myelin layer.
OBJECTIVE: To examine the effect of multidisciplinary ALS care on the quality-of-life (QoL) in patients with ALS and their caregivers. METHODS: In a cross-sectional study, 208 patients with ALS and their caregivers were interviewed. QoL was assessed using the 36-item Short Form Health Survey (SF-36) and two visual analogue scales (VAS). Criteria for multidisciplinary ALS care were: an ALS team headed by a consultant in rehabilitation medicine and consisting of at least a physical therapist, occupational therapist, speech pathologist, dietician and a social worker; use of the Dutch ALS consensus guidelines for ALS care; and at least six incident ALS patients per year. RESULTS: Clinical characteristics and functional loss of the 133 patients receiving multidisciplinary ALS care and the 75 patients receiving general ALS care were similar. The percentage of patients with adequate aids and appliances was higher in those with multidisciplinary ALS care (93.1 vs 81.3%, p = 0.008), whereas the number of visits to professional caregivers was similar in both groups. Patients in the multidisciplinary ALS care group had a better mental QoL on the SF-36 Mental Summary Score than those in the general care group (p = 0.01). The difference in QoL was most pronounced in the domains of Social Functioning and Mental Health, and was independent of the presence of aids and appliances. No significant differences were found in the SF-36 Physical Summary Score, VAS, or in QoL of caregivers of patients with ALS. CONCLUSION: High standard of care improves mental quality-of-life in patients with ALS.
This guideline presents recommendations for the diagnosis and treatment of dermatomyositis, polymyositis and sporadic inclusion body myositis (sIBM) according to the best available evidence. Characteristic skin abnormalities can be sufficient for the diagnosis of dermatomyositis. In case of doubt, a skin biopsy is advisable. A muscle biopsy is indicated when other examinations are inconclusive and the musculature is involved. The working group considers screening for cancer to be required in adults with dermatomyositis and presents recommendations for the way that this should be done. At least one-third of all patients with polymyositis has, or will develop, an associated inflammatory connective tissue disease. If a patient with a connective tissue disease develops symmetrical, proximal muscle weakness in the course of weeks or months, this may be assumed to be due to polymyositis. In the absence ofpre-existing connective tissue disease, demonstration of a mononuclear cell infiltrate in muscle tissue is a prerequisite for the diagnosis ofpolymyositis. The histopathology of muscle tissue is used as the gold standard for the diagnosis of sIBM. The practice guideline presents criteria for the concept 'activity' of myositis. Disease activity serves as a guideline for the treatment of polymyositis and dermatomyositis. The treatment of choice for dermatomyositis and polymyositis is high-dose prednisone. Physical activity does not have a negative effect on the course of these diseases. The long-term prognosis ofdermatomyositis and polymyositis is not well known. The clinical course of sIBM is slowly progressive.
BACKGROUND: Laing early onset distal myopathy (MPD1) is an autosomal dominant myopathy caused by mutations within the slow skeletal muscle fibre myosin heavy chain gene, MYH7. It is allelic with myosin storage myopathy, with the commonest form of familial hypertrophic cardiomyopathy, and with one form of dilated cardiomyopathy. However, the clinical picture of MPD1 is distinct from these three conditions. OBJECTIVE: To collate and discuss the histological features reported in the muscle biopsies of MPD1 patients and to outline the clinical features. RESULTS: The phenotype of MPD1 was consistent, with initial weakness of great toe/ankle dorsiflexion, and later development of weakness of finger extension and neck flexion. Age of onset was the only variable, being from birth up to the 20 s, but progression was always very slow. The pathological features were variable. In this retrospective series, there were no pathognomonic diagnostic features, although atrophic type I fibres were found in half the families. Rimmed vacuoles are consistently seen in all other distal myopathies with the exception of Myoshi distal myopathy. However, they were found in a minority of patients with MPD1, and were not prominent when present. Immunohistochemical staining for slow and fast myosin showed co-expression of slow and fast myosin in some type I fibres, possibly indicating a switch to type II status. This may be a useful aid to diagnosis. CONCLUSIONS: The pathological findings in MPD1 are variable and appear to be affected by factors such as the specific muscle biopsied, the age of the patient at biopsy, and the duration of disease manifestations.
BACKGROUND: Dominant mutations in COL6A1, COL6A2, and COL6A3, the three genes encoding collagen type VI, a ubiquitous extracellular matrix protein, are associated with Bethlem myopathy (BM) and Ullrich scleroatonic muscular dystrophy. METHODS: The authors devised a method to screen the entire coding sequence of the three genes by reverse transcriptase-PCR amplification of total RNA from skin fibroblasts and direct sequencing of the resulting 25 overlapping cDNA fragments covering 107 exons. RESULTS: Four splicing and four missense mutations were identified in 16 patients with BM, six of which are novel mutations in COL6A1. Both common and private mutations are localized in the alpha1 (VI) chain between the regions corresponding to the 3' end of the NH2-globular domain and the 5' end of the triple helix, encoded by exons 3 through 14. CONCLUSIONS: The clustering of the mutations in a relatively narrow area of the three collagen type VI chains in patients with Bethlem myopathy (BM) suggests that mutations in different regions could result in different phenotypes or in no phenotype at all. Moreover, the detection of mutations in only 60% of the patients suggests the existence of at least another gene associated with BM. The authors propose the direct sequencing of COL6 cDNAs as the first mutation screening analysis in BM, given the high number of exon-skipping events.
A consensus development meeting was held to evaluate whether or not in the Netherlands all requirements were fulfilled for implementation of population screening with FOBT for colorectal cancer, or whether consensus was present that fulfilment by additional research or organisational actions could be obtained within 2-3 years. There was consensus that all classical Wilson and Jungner (1968) criteria, and six additional ones added more recently, had already been fulfilled or could be fulfilled within 2-3 years. Consequently, it was concluded that a national population screening for colorectal cancer should be implemented and carried out in the Netherlands in line with current national and European cancer screening programmes. A list of organisational actions to be taken was established. Research that is needed before the actual national launch of the screening within 2-3 years has been defined. Priorities have to be set for research and organisational actions for the coming 2-3 years for the implementation of population screening. In addition, research suggestions have been defined for the next 10-15 years for evaluation and/or improvement of implemented FOBT screening, and for future screening methodology. It was considered essential that infrastructure for future research would be embedded in the screening programme. A project group to arrange this should be formed.
Whether autoimmune mechanisms play a role in the pathogenesis of inclusion body myositis (IBM) is unknown. Human leukocyte antigen (HLA) analysis in 52 patients, including 17 with autoimmune disorders (AIDs), showed that patients were more likely to have antigens from the autoimmune-prone HLA-B8-DR3 ancestral haplotype than healthy control subjects, irrespective of the presence of AIDs. Patients lacked the apparently protective HLA-DR53 antigen. The results provide further support for an autoimmune basis in IBM.
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BACKGROUND: According to widely used criteria (Bohan and Peter criteria, 1975), dermatomyositis (DM) is differentiated from polymyositis (PM) only by skin changes. More recent criteria also include histopathologic characteristics enabling the distinction between PM and DM and the differentiation of sporadic inclusion body myositis (s-IBM) from PM. The authors investigated the applicability of diagnostic features for diagnosing PM and DM. METHODS: The authors performed a retrospective follow-up study of 165 patients with 1) a previous diagnosis of myositis; 2) subacute onset of symmetric, proximal weakness; and 3) an evaluation between 1977 and 1998 excluding other neuromuscular disorders. RESULTS: The diagnoses at initial evaluation based on clinical, laboratory, and histopathologic criteria were PM, 9 (5%); DM, 59 (36%; 54 isolated, 3 with associated connective tissue disease [CTD], 2 with associated malignancy); unspecified myositis (perimysial/perivascular infiltrates, no PM or DM), 65 (39%; 38 isolated myositis, 26 with associated CTD, 1 with malignancy); and possible myositis (necrotizing myopathy, no inflammatory infiltrates), 32 (19%; 29 isolated myositis, 3 with associated CTD). At follow-up evaluation, five of the nine patients with PM had typical s-IBM features. None of the remaining four patients complied with the assumed typical signs of PM. Ten of the 38 patients with isolated unspecified myositis had been diagnosed with a CTD. CONCLUSIONS: Polymyositis is an overdiagnosed entity. At evaluation, more than half the patients with autoimmune myositis cannot be specifically diagnosed with polymyositis or dermatomyositis. A quarter of patients with isolated unspecified myositis subsequently developed connective tissue disease.
Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with beta-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 degrees C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with (111)In to a high specific activity. The (111)In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the (111)In-labelled analogues at 37 degrees C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this (111)In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the (111)In-labelled DTPA- and DOTA-conjugated NT analogues are excellent candidates for imaging and therapy of exocrine pancreatic cancer, peptide 2530 being the most promising analogue.
This review discusses the most important lower motor neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom motor neurons (lower motor neuron disease (LMND)) are primarily affected or motor axons and their surrounding myelin (multifocal motor neuropathy (MMN)), both leading to muscle atrophy and weakness. Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation.MMN is a lower motor neuron syndrome with presumed immunemediated pathogenesis. Evidence of motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower motor neuron syndromes. For the individual patient, distinction between the various lower motor neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.
OBJECTIVE: To evaluate the clinical features, muscle pathology and response to treatment in patients with a necrotising myopathy, without mononuclear cell infiltrates. BACKGROUND: Mononuclear cell infiltrates in the muscle biopsy specimen are the diagnostic hallmark of the immune-mediated idiopathic inflammatory myopathies (IIM). In patients with the typical clinical features of IIM, absence of these infiltrates in the muscle biopsy specimen casts doubt on the diagnosis and leads to uncertainty about therapeutical strategies. METHODS: A detailed description is given of the clinical, laboratory, and histopathological features of eight patients suspected of having an idiopathic inflammatory myopathy, in whom mononuclear cell infiltrates in their muscle biopsy specimens were lacking. RESULTS: Eight patients (five men, three women, age range 40-69 years) had severe, symmetrical proximal weakness with a subacute onset. There were no skin abnormalities suggesting dermatomyositis. Serum creatine kinase activity was more than 10 times elevated. Repeated muscle biopsy specimens, taken from a symptomatic muscle prior to immunosuppressive treatment showed widespread necrosis, regeneration, and atrophy of muscle fibres, but no mononuclear cell infiltrates. Known causes of necrotising myopathy were excluded. Three patients had a malignancy. Adequately dosed and sustained immunosuppressive treatment eventually resulted in normal or near normal muscle strength in seven patients. One patient showed marked improvement. CONCLUSION: Occasionally, patients who clinically present as an idiopathic inflammatory myopathy may lack mononuclear cell infiltrates in their muscle biopsy specimens. This subacute-onset progressive necrotising myopathy should not deter the clinician from timely and appropriate treatment as we consider this myopathy to be steroid-responsive with a possible immune-mediated pathogenesis.
We describe a patient with somatic mosaicism of a point mutation in the dystrophin gene causing benign muscular dystrophy with an unusual asymmetrical distribution of muscle weakness and contractures. To our knowledge this is the first patient with asymmetrical weakness and contractures in an ambulatory patient with a dystrophinopathy.
Context. Maximal voluntary isometric contraction, a method quantitatively assessing muscle strength, has proven to be reliable, accurate and sensitive in amyotrophic lateral sclerosis. Hand-held dynamometry is less expensive and more quickly applicable than maximal voluntary isometric contraction. Objective. To investigate if hand-held dynamometry is as reliable and valid as maximal voluntary isometric contraction in measuring muscle strength in patients with an adult-onset, non-hereditary progressive lower motor neuron syndrome. Design. Two testers performed maximal voluntary isometric contraction and hand-held dynamometry measurements in six muscle groups bilaterally in patients with progressive lower motor neuron syndrome to assess reliability and validity of both the methods. Setting. Outpatient units of an academic medical center. Patients. A consecutive sample of 19 patients with non-hereditary progressive lower motor neuron syndrome (median disease duration 32.5 months, range 10-84) was tested. Outcome measures. Comparison between maximal voluntary strength contractions as measured by hand-held dynamometry and maximal voluntary isometric contraction. Results. Low intra- and interrater variation in all muscle groups were found, intraclass correlation coefficients vary between 0.86 and 0.99 for both methods. Both methods correlated well in all muscle groups with Pearson's correlation coefficients ranged between 0.78 and 0.98. Scatter plots indicated a trend to under-estimate muscle strength above 250 N by hand-held dynamometry as compared with maximal voluntary isometric contraction. Conclusions. For longitudinal evaluation of muscle strength in patients with progressive lower motor neuron syndrome (i.e. between 0 and 250 N), muscle strength can be accurate quantified with both hand-held dynamometry and maximal voluntary isometric contraction. Hand-held dynamometry has the advantage of being cheap and quickly applicable. However, our results indicate that hand-held dynamometry is less sensitive than maximal voluntary isometric contraction in detecting subnormal muscle strength in strong muscle groups (i.e. >250 N), due to limited strength of the tester.
OBJECTIVES: To assess the reliability of quantitative assessment of vibration sense with a Vibrameter type III. MATERIAL AND METHODS: We examined 111 healthy subjects (21-69 years). For intraobserver reliability, short-term (15 min between measurements) (n=11) and 24-h (n=28) reliability was tested. For interobserver reliability, a second tester performed the second measurement 15 min after the initial test (n=39). We also assessed the independent impact of effects of age, gender and height on vibration thresholds. RESULTS: In our study the intraobserver reliability is good [intraclass correlation coefficients (ICC) ranging from 0.55 to 0.99], whereas the interobserver reliability is moderate (ICC ranging from 0.32 to 0.88). Multiple linear regression analysis showed that age and--to a lesser extent--height was independently associated with the threshold values of the feet, but not with the thresholds of the hands. CONCLUSION: The use of a Vibrameter for measuring vibration thresholds in clinical practice and in multicentre studies is restricted because of the moderate interobserver reliability.