Cardiac rhabdomyomas and their association with tuberous sclerosis

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.     

Fructosamine and glycated haemoglobin in the assessment of long term glycaemic control in diabetes

Fructosamine and glycated haemoglobin were measured simultaneously in 147 children with diabetes. If glycated haemoglobin is considered as the 'gold standard' for long term glycaemic control, then fructosamine is a poor indicator of actual glycated haemoglobin values, with wide 95% confidence (fiducial) limits. This shows that it is impossible to accurately predict glycated haemoglobin concentrations and therefore, by implication, longer term glycaemic control, from measurements of fructosamine. As the major studies on the prevention of microvascular complications in diabetes have used glycated haemoglobin levels to assess glycaemic control, it is suggested that this measurement should be used in all children with diabetes in preference to the measurement of fructosamine.     

Natural history of trisomy 13

The poor prognosis of patients with trisomy 13 has long been accepted and has been ascribed to brain and heart malformations. It has been suggested, however, that the long term survival is better than was previously thought and that cardiac surgery may be justified. This population based study reviews the incidence, antenatal diagnosis, spectrum of survival from congenital heart disease, and mode of death for patients with trisomy 13 in the Northern Health Region from 1985 to 1992. There was an observed prevalence at birth of 0.049/1000 live births and an expected prevalence, allowing for antenatal diagnosis, of 0.077. None of the cardiac lesions found would cause early death. The median survival in this series was four days; the longest survival was 3.5 months. The principal mode of death was apnoea in 14 of 16 children, irrespective of the presence of a cranial abnormality. In the light of these findings, cardiac surgery cannot be justified in patients with trisomy 13.     

Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes

Transneuronal degeneration of retinal ganglion cells was directly demonstrated in a patient who had unilateral removal of the striate cortex forty years prior to necropsy. For comparison, another case is presented showing anterograde transneuronal atrophy forty years after enucleation of one eye.     

Frequent detection of thyroid peroxidase-specific IgG+ memory B cells in blood of patients with autoimmune thyroid disease

Centrocytes in germinal centers on selection differentiate into plasma cells and/or memory B cells. Cells that have acquired autoreactivity by somatic mutation generally fail to undergo positive selection and die by apoptosis. Presence of isotype-switched high-affinity autoantibodies in serum of autoimmune patients suggests that autoreactive plasma cells eventually emerge from a germinal center reaction. Currently, it is still unclear to which extent the same is true for autoreactive memory B cells. To address this question, we have analyzed whether IgG-bearing memory B cells with specificity for thyroid peroxidase (TPO) can be found in blood of patients with autoimmune thyroid disease and in normal blood donors. Autoreactive TPO-specific IgG+ memory B cells were identified using a previously described assay combining two-step immunomagnetic enrichment with flow cytometric detection. Autoreactive IgG+ memory B cells were found in 65% of the patients with autoimmune thyroid disease and in 17% of normal blood donors; 40% of the latter had no detectable TPO-specific IgG in the serum. The specificity of enriched TPO-specific IgG+ memory B cells was confirmed by in vitro proliferation and differentiation into antibody-secreting cells at limiting dilution and analysis of the supernatants for the presence of TPO-specific IgG. Detection of TPO-specific IgG+ memory B cells in most patients with clinically manifested autoimmune thyroid disease and few normal blood donors may argue for a role of circulating memory B cells in onset of disease.     

Plasma levels of cellular fibronectin in diabetes

OBJECTIVE: Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Elevated plasma levels of cellular fibronectin therefore reflect loss of endothelial cell polarization or injury to blood vessels. Consequently, elevated plasma levels of circulating cellular fibronectin have been described in clinical syndromes with vascular damage, although not in diabetes or atherosclerosis. RESEARCH DESIGN AND METHODS: We determined fibronectin levels in 52 patients with type 1 diabetes, 50 patients with type 2 diabetes, 54 patients with a history of ischemic stroke, 23 patients with renal artery stenosis, and 64 healthy subjects. RESULTS: Circulating cellular fibronectin was significantly elevated in patients with diabetes (4.3 +/- 2.8 microg/ml) compared with patients with ischemic stroke (2.0 +/- 0.9 microg/ml), patients with renovascular hypertension (1.7 +/- 1.1 microg/ml), and healthy subjects (1.4 +/- 0.6 microg/ml). Patients with diabetes and at least one cardiovascular risk factor had an almost 2.5-fold increase in cellular fibronectin compared with diabetic subjects without such a risk factor. In multivariate regression analysis, higher triglycerides, current or past cigarette smoking, and higher urinary albumin excretion were independently associated with an increase in circulating cellular fibronectin in diabetes. CONCLUSIONS: These results suggest that circulating cellular fibronectin may be a marker protein for endothelial cell activation, especially in diabetes. Prospective studies are needed to explore this possibility