Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF-B in myelinating tracts

Platelet-derived growth factor (PDGF) influences the generation of neurons and glia during embryogenesis and in early postnatal life. In an attempt to determine the consequences of an overexpression of PDGF-B during the first weeks of life, we targeted transgenic expression of a human PDGF-B cDNA to myelinating tracts using the promoter region of the myelin basic protein (MBP) gene. Transgenic mRNA and protein were expressed in the brain and the expression profile of the human PDGF-B during early postnatal development closely paralleled that of the endogenous mouse MBP gene. The gross morphological appearance of transgenic brains was normal but at the cellular level several phenotypic alterations could be identified. In white matter tracts such as the corpus callosum and cerebellar medulla, there was a marked hypercellularity. The number of oligodendrocyte precursors was increased and astrocytes were more abundant. In adult mice carrying the MBP-PDGF-B transgene, however, myelination appeared normal and the amount of oligodendrocytes was similar to that of control littermates. In addition to the phenotypic alterations in the brain, investigation of eye structure revealed a striking disorganization of retinal architecture. The retina was folded with cells collected in papillar or follicular-like structures. Retinal whole mount preparations after India ink perfusion revealed capillary disorganization with large-caliber vessels supporting only a few fine branches. Our observations strengthen the notion that PDGF is an important effector molecule in postnatal CNS development.     

Mitochondrial dysfunction in myofibrillar myopathy

'Myofibrillar myopathy' defines a myopathic condition with focal myofibrillar destruction and accumulation of degraded myofibrillar elements. Despite the fact that a number of mutations in different genes as well as cytotoxic agents lead to the disease, abnormal accumulation of desmin is a typical, common feature. Pathological changes of mitochondrial morphology and function have been observed in animal models with intermediate filament pathology. Therefore, in the present study we tested for mitochondrial pathology in skeletal muscle of five patients with the pathohistological diagnosis of myofibrillar myopathy. Screening for large-scale mtDNA deletions and the frequent MERRF (myoclonic epilepsy; ragged red fibres) and MELAS (mitochondrial encephalomyopathy; lactic acidosis; stroke) point mutations was negative in all patients. Histologically, all muscle biopsies showed nonspecific abnormalities of the oxidative/mitochondrial enzyme stainings (histochemistry for reduced nicotinamide adenine dinucleotide, succinic dehydrogenase, cytochrome c oxidase), only one of them had ragged red fibres and a significant number of cytochrome c oxidase-negative fibres. Upon biochemical investigation, four of our patients showed pathologically low respiratory chain complex I activities. Only one of our patients had a pathologically low complex IV activity, while the measurements of the others were within low normal range. The single patient with pathological values for both complex I and IV was the one with the clear histological hallmarks (ragged red and cytochrome c oxidase-negative fibres) of mitochondrial pathology. She also was the only patient with clinical signs hinting at a mitochondrial disorder. Together with data from observations in desmin- and plectin-deficient mice, our results support the view that desmin intermediate filament pathology in these cases is closely linked to mitochondrial dysfunction in skeletal muscle.     

Peak nasal inspiratory and expiratory flow measurements--practical tools in primary care?

General practitioners diagnose and treat numerous patients with nasal problems but have no objective equipment to aid diagnosis. We studied the characteristics of peak nasal inspiratory (PNIF) and expiratory (PNEF) flows to explore their utility for primary care use. One hundred healthy volunteers, 50 men, 50 women, performed PNIF and PNEF measurements in standardised laboratory circumstances. Repeatability was tested for a subgroup of 20 women who performed two consecutive series of PNIF and PNEF at a 2-minute interval. Diurnal variability was tested with a subgroup of 10 men and 10 women who recorded PNIF and PNEF values at home every morning and evening for 7 days. Distribution of individual values for both PNIF and PNEF was wide and independent of subject's age, height, or gender. Repeatability was poor and diurnal variation substantial. PNIF and PNEF lack the properties of good clinical tests and thus cannot be recommended for primary care use.     

Physical performance tests for people with spinal pain--sensitivity to change

Objective : The sensitivity to change for six physical performance tests for assessing impairments and activity limitations in persons with spinal pain was examined.

Method : Eighty men and 106 women with long-term spinal pain participating in a randomized controlled study went through the tests on inclusion in the study, and were then invited to follow-up tests after 5 weeks and 6 months. The tests were a 'step-on-stool test', three gait tests and two lifting tests (PILE tests). Sensitivity to change was examined by relating changes in physical performance to self-rated concepts assumed to reflect a real change in the individual. Effect sizes were calculated.

Results : Sensitivity to change in absolute values was revealed for the gait test with burden, the stair-climbing test and the PILE cervical test for women. Only the PILE cervical test showed responsiveness to clinically important change according to our criteria. Moderate to high effect sizes were found for all tests. Relatively few subjects improved to an extent considered clinically important. Improvement was greater in subjects whom inclusion measurements showed to be less fit.

Conclusions : The sensitivity to change was moderate over a 6-month period for the physical performance tests. The gait test with burden, the stair-climbing test and the PILE tests were most sensitive to change. It is suggested that these tests be incorporated in an 'assessment instrument bank' for physiotherapists, supplemented with other reliable and valid tests relevant to the problems for the individual with spinal pain.