Life expectancy in British Marfan syndrome populations

A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome.     

Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes

Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.      

Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition

Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders. However, fundamental questions remain about the effects of DBS on neurons surrounding the electrode. Experimental studies have produced apparently contradictory results showing suppression of activity in the stimulated nucleus, but increased inputs to projection nuclei. We hypothesized that cell body firing does not accurately reflect the efferent output of neurons stimulated with high-frequency extracellular pulses, and that this decoupling of somatic and axonal activity explains the paradoxical experimental results. We studied stimulation using the combination of a finite-element model of the clinical DBS electrode and a multicompartment cable model of a thalamocortical (TC) relay neuron. Both the electric potentials generated by the electrode and a distribution of excitatory and inhibitory trans-synaptic inputs induced by stimulation of presynaptic terminals were applied to the TC relay neuron. The response of the neuron to DBS was primarily dependent on the position and orientation of the axon with respect to the electrode and the stimulation parameters. Stimulation subthreshold for direct activation of TC relay neurons caused suppression of intrinsic firing (tonic or burst) activity during the stimulus train mediated by activation of presynaptic terminals. Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon. This independence of firing in the cell body and axon resolves the apparently contradictory experimental results on the effects of DBS. In turn, the results of this study support the hypothesis of stimulation-induced modulation of pathological network activity as a therapeutic mechanism of DBS.     

Noncultivable viruses and neonatal diarrhea: fifteen-month survey in a newborn special care nursery.

During a 15-month period of surveillance, diarrhea developed in 257 of 913 babies (28%) admitted within 2 hours of birth to a special care nursery in Melbourne, Australia. Diarrhea was seasonal, affecting a maximum of 43% of babies admitted during one winter month (July) and a minimum of 13% of babies admitted during one summer month (December). Diarrhea was no more frequent nor more severe in babies of very low birth weight or of very early gestational age. Two noncultivable viruses were located by electron microscopy in feces from babies with or without diarrhea. Excretion of a reovirus-like particle (rotavirus, duovirus, human reovirus-like agent, infantile gastroenteritis virus) was temporally related to diarrheal symptoms. Asymptomatic infection with this virus also occurred. A 28-nm virus-like particle was excreted by some babies, but it could not be implicated on epidemiological grounds in the etiology of the diarrhea. Rotavirus infection may be an important cause of endemic diarrhea in nurseries for the newborn. Infection may be difficult to control or eradicate, since it is often asymptomatic and may be influenced by infection in the community at large.     

Interoception: the inside story--a model for psychosomatic processes

OBJECTIVE: To comprehend psychosomatic processes, it will be necessary to understand the brain's influences on bodily functions and also the body's afferent sensory input to the central nervous system, including the effects of this input on behavior and cognitive functions, especially emotion. The objective of this Presidential Address is to review what is known circa the year 2000 of the processes and mechanisms of visceral sensory psychobiology, often called interoception. METHODS: Over 1000 publications that have appeared since the 19th century were reviewed to prepare this review, including a group that are specifically cited here. RESULTS: Factors and data were reviewed that were identified as germane to understanding interoception. These included definitional issues, historical roots, the neural basis, studies and results in the cardiovascular-respiratory and alimentary-gastrointestinal systems, studies of emotion, and studies in people with mental disorders. Drug and hormone effects, pain, proprioception, and phantom limb or organ factors, and the role of awareness were briefly described. Methodological issues, methods of study including functional imaging, and possible future directions for study were identified. CONCLUSIONS: Understanding the physical basis of psychosomatic processes, including the so-called mind-body problem, will require a detailed understanding the psychobiology of interoception.     

Trial of platelet-derived growth factor antagonist,trapidil, in accelerated nephrotoxic nephritis in the rabbit.

The platelet-derived growth factor (PDGF) antagonist, trapidil, which also blocks the thromboxane and/or PG-endoperoxide receptor and is an inhibitor of thromboxane synthetase, was administered during rabbit accelerated nephrotoxic nephritis; the clinical and histological evolution was studied as well as urinary immunoreactive thromboxane (i-TXB2) and immunoreactive prostaglandin E2 (i-PGE2) excretion. Although the dose we used has been shown to be effective in vivo, and it inhibited the urinary i-TXB2 excretion on days 5 and 10, it neither inhibited the enhanced production of i-TXB2 on day 1, nor prevented the glomerular influx of monocytes on days 5 and 10. All clinical and histological data tend to be worse rather than better in trapidil-treated animals on days 5 and 10.