ABSTRACT
To identify serum biomarkers that allow monitoring of disease progression and treatment effects in Duchenne muscular dystrophy (DMD) patients, levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and osteopontin (OPN) were determined in 63 DMD patients on corticosteroid therapy. These proteins were selected for their role in the pathogenesis of muscular dystrophy. Levels of MMP-9 and TIMP-1 were significantly higher in sera of DMD patients compared to healthy controls, whereas the OPN levels showed no significant difference. MMP-9 levels were also observed to be significantly higher in older, nonambulant patients, compared to ambulant patients. Longitudinal data from a smaller cohort of DMD patients followed up for over 4years showed that MMP-9, but not TIMP-1 increased significantly with age. Hence, MMP-9 is a potential DMD biomarker for disease progression. Future studies have to confirm whether serum MMP-9 levels can be used to monitor therapeutic response.
Subject(s)
Disease Progression , Matrix Metalloproteinase 9/blood , Muscular Dystrophy, Duchenne/blood , Muscular Dystrophy, Duchenne/physiopathology , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Animals , Biomarkers/blood , Case-Control Studies , Child , Child, Preschool , Disease Models, Animal , Female , Humans , Longitudinal Studies , Male , Mice , Mice, Inbred C57BL , Mice, Inbred mdx , Muscular Dystrophy, Duchenne/drug therapy , Osteopontin/blood , Tissue Inhibitor of Metalloproteinase-1/blood , Treatment Outcome , Young AdultABSTRACT
Myoglobinuria is a recognised complication of Duchenne muscular dystrophy (DMD), but has only once been reported in ambulant boys on corticosteroid therapy [Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Remission of clinical signs in early Duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Eur J Paediatr Neurol 2002;6(3):153-9.]. We present three prednisolone-treated boys with myoglobinuria and in two cases this was recurrent. All three showed improved motor performance in response to the introduction of corticosteroids. The greater activity of steroid-treated individuals may place their dystrophin-deficient muscles under greater mechanical stress, predisposing to further muscle fibre damage and consequent myoglobinuria. Families and physicians need to have an increased awareness of this possibility and of the appropriate management of myoglobinuria.
Subject(s)
Adrenal Cortex Hormones/adverse effects , Exercise Therapy/adverse effects , Muscle, Skeletal/drug effects , Muscular Dystrophy, Duchenne/complications , Muscular Dystrophy, Duchenne/drug therapy , Myoglobinuria/chemically induced , Child , Humans , Male , Motor Activity/physiology , Movement/physiology , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Duchenne/physiopathology , Myoglobin/metabolism , Myoglobinuria/pathology , Myoglobinuria/physiopathology , Prednisolone/adverse effects , Rhabdomyolysis/chemically induced , Rhabdomyolysis/pathology , Rhabdomyolysis/physiopathology , Stress, Mechanical , Treatment Outcome , Withholding TreatmentABSTRACT
OBJECTIVES: Our aims were to investigate family medical history taking in general practice, and to evaluate the value attached to the family medical history as an aid to decision making in general practice. METHOD: A postal questionnaire survey was conducted among all 291 GPs working within the Calderdale and Kirklees Health Authority area. Each questionnaire was followed by a reminder. The main outcome measures were answers to questions on routine and opportunistic family history taking and a question about transmitting knowledge about genetic risk to other members of the family. Questions were also posed about the value attached to the family medical history as an aid to decision making. RESULTS: A total of 193 GPs returned the questionnaire (response rate 66.3%). On registration, 94.3% of GPs indicated that enquiries were made about a family history of coronary heart disease. Breast and colorectal cancer were specifically asked about by 48.4% and 30.7% of GPs, respectively. One-fifth of respondents indicated that they asked a general question about family medical history. A little over one-quarter of respondents indicated that they made opportunistic enquiries about the family history or suggested that the patient should inform other members of the family about possible risks. In the scenarios highlighted in this study, the majority of respondents felt that the family medical history had value as an aid to decision making. This was particularly the case for checking a patient's cholesterol (92.1%) and for initiating referrals in younger patients with possible cancer-related symptoms (three-quarters of respondents). CONCLUSION: GPs value the family medical history as an aid to decision making. Unfortunately, apart from enquiries about coronary heart disease, routine or opportunistic family history taking is not occurring in practice. Mechanisms need to be sought to extract information from the family medical history so that it can be more effectively used by GPs.
