The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessive disorders. A new pathomechanism has recently been identified in a group of these disorders in which known or putative glycosyltransferases are defective. Common to all these conditions is the hypoglycosylation of alpha-dystroglycan. Fukuyama CMD, muscle-eye-brain disease and Walker-Warburg syndrome, each associated with eye abnormalities and neuronal migration defects, result from mutations in fukutin, POMGnT1 and POMT1, respectively, while mutations in the fukutin-related protein (FKRP) gene cause congenital muscular dystrophy 1C, typically lacking brain involvement. Another putative glycosyltransferase, Large, is mutated in the myodystrophy mouse. The human homologue of this gene is therefore a strong candidate for involvement in novel forms of muscular dystrophy. We studied 36 patients with muscular dystrophy and either mental retardation, structural brain changes or abnormal alpha-dystroglycan immunolabelling, unlinked to any reported CMD loci. Linkage analysis in seven informative families excluded involvement of LARGE but sequencing of this gene in the remaining 29 families identified one patient with a G1525A (Glu509Lys) missense mutation and a 1 bp insertion, 1999insT. This 17-year-old girl presented with congenital muscular dystrophy, profound mental retardation, white matter changes and subtle structural abnormalities on brain MRI. Her skeletal muscle biopsy showed reduced immunolabelling of alpha-dystroglycan. Immunoblotting with an antibody to a glycosylated epitope demonstrated a reduced molecular weight form of alpha-dystroglycan that retained some laminin binding activity. This is the first description of mutations in the human LARGE gene and we propose to name this new disorder MDC1D.
Aims/hypothesisWe aimed to examine the effects of bariatric surgery on microvascular complications in patients with type 2 diabetes using objective measures.MethodsProspective case–control study of 70 obese surgical patients with type 2 diabetes undergoing gastric bypass surgery matched for age, sex and duration of diabetes to 25 medical patients treated using international guidelines. Microvascular complications were assessed before and 12–18 months after intervention using urine albumin creatinine ratio (ACR) measurements, two-field digital retinal images and peripheral nerve conduction studies (in the surgical group only).ResultsUrine ACR decreased significantly in the surgical group but increased in the medical group. There were no significant differences between the surgical and medical groups in the changes in retinopathy. There were no changes in the nerve conduction variables in the surgical group.Conclusions/interpretationIn the short term, bariatric surgery may be superior to medical care in the treatment of diabetic nephropathy, but not retinopathy or neuropathy.
Objectives-To investigate visual function in migraine using visual evoked potentials. Methods-Electroretinograms(ERGs) and visual evoked potentials (VEPs) to single flash (SF) and pattern reversal (PR) stimuli were studied in 92 migraine subjects and 62 controls. Results-In subjects with migraine, ERGs to single flash were normal. Mean latencies of the P1 and P2 waves in the SFVEP were increased at the occiput by 6% and 4% respectively, but normal at the vertex. Mean latency of the P100 wave in the PRVEP was increased by 5%. These increases were not related to the presence or absence of an aura or to the duration of migraine. P100 amplitude showed a more complex abnormality. It was increased in migraine without aura by 23% compared with controls, regardless of duration of migraine. In migraine with aura it was similarly increased, by 23%, in cases of short duration, but in addition it showed a sharp decline with duration. In cases with a duration of 30 or more years it was 36% less than in cases of short duration, and 21% less than in controls. Conclusions-Subjects with migraine have constitutionally prolonged VEP latencies and increased P100 amplitude, but the latter declines to below normal in cases with a long history of migraine with aura. This decline may reflect subtle neuronal damage within the visual system from repeated transient ischaemia experienced during the aura. Future electrophysiological and other studies will need to be controlled for duration of migraine history. The studies reported here formed part of a PhD project 4 in which visual function was studied in 92 subjects with migraine and 62 controls, by neurophysiological and psychophysical methods. Here we report the results of investigation by electroretinogram (ERG), SFVEP, and PRVEP. Some preliminary data have already been published. Methods SUBJECTSThe patients in this study were not a random sample of the migraine population. They came from a wide age range, and there was a deliberate selection for those with a visual aura and with attacks precipitated by visual stimuli, to provide subgroups large enough for meaningful comparisons. Controls were found among colleagues, the spouses, or friends of subjects with migraine, and other volunteers. All subjects had a visual acuity of 6/6 or better, and none of them had any visual disorder.All 92 subjects fulfilled the International Headache Society (IHS) criteria for a diagnosis of migraine with or without aura.7 There were 72 women and 20 men, aged 16-59 years (mean 40.2 (SD 12.5) years). All were free of headache at the time of testing, and none were taking prophylactic treatment. Forty seven had migraine with aura (MA), 37 had migraine without aura (MO), and eight had both. Results from these eight patients have been included only when the whole migraine group is considered. All patients with MA had a visual aura, and seven also had other aura symptoms. Seventy three patients reported attacks triggered by visual stimuli, such as bright lights, flashing lights, or patterns. Migraine ...
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