Biomedical subjects

Paul D Griffiths

Publications and source records attributed to Paul D Griffiths.

60 records · Page 4Linked to original sources

PubMed2002

Strategies to prevent CMV infection in the neonate.

Congenital cytomegalovirus (CMV) infection is a major cause of sensorineural hearing loss and mental retardation, whose annual healthcare costs in the USA approximate to one billion dollars. Only a minority of neonates with this infection has symptoms present at birth and some of the damage to ear and brain occurs in the first few months of life. Extensive studies of CMV infection have been conducted in pregnant women and their children to define the natural history of this infection. What is required now is a concerted commitment to tackle this clinical problem using one or more of the following strategies: avoid iatrogenic transmission; advise those at risk how to avoid acquisition; provide diagnosis in an individual neonate or pregnant woman and offer treatment; develop and deploy a CMV vaccine.

Cytomegalovirus Infections↗

PubMed2002

Resistance in viruses other than HIV.

The aim of this brief paper is to summarize the ways in which viruses develop resistance to currently licensed anti-viral drugs and to comment on their clinical relevance. Specific examples will be chosen to emphasize basic principles of the development of resistance and readers are referred elsewhere to a summary of resistance in HIV that follows the same principles.

Antiviral Agents↗

PubMed2002

Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex.

Tuberous sclerosis is one of the few established medical causes of autism spectrum disorder and is a unique neurogenetic model for testing theories about the brain basis of the syndrome. We conducted a retrospective case study of the neuro-epileptic risk factors predisposing to autism spectrum disorder in individuals with tuberous sclerosis to test current neurobiological theories of autism spectrum disorder. We found that an autism spectrum disorder diagnosis was associated with the presence of cortical tubers in the temporal but not other lobes of the brain. Indeed, the presence of tubers in the temporal lobes appeared to be a necessary but not sufficient risk factor for the development of an autism spectrum disorder. However, contrary to the predictions of some theories, the location of tubers in specific regions of the temporal lobe, such as the superior temporal gyrus or the right temporal lobe, did not determine which individuals with temporal lobe tubers developed an autism spectrum disorder. Instead, outcome was associated with various indices of epileptic activity including evidence of temporal lobe epileptiform discharges on EEG, the age to onset of seizures in the first 3 years of life and a history of infantile spasms. The results indicated that individuals with tuberous sclerosis are at very high risk of developing an autism spectrum disorder when temporal lobe tubers are present and associated with temporal lobe epileptiform discharges and early-onset, persistent spasm-like seizures. These risk markers constitute useful clinical indicators of prognosis, but further research is required to identify the neurobiological mechanisms responsible for their association with outcome. Most especially, it will be important to test whether, as the findings suggest, there is a critical early stage of brain maturation during which temporal lobe epilepsy perturbs the development of brain systems that underpin 'social intelligence' and possibly other cognitive skills, thereby inducing an autism spectrum disorder.

Autistic Disorder↗

PubMed2002

The 2001 Garrod lecture. The treatment of cytomegalovirus infection.

This named lecture provides an opportunity to take an historical perspective on cytomegalovirus (CMV) infection. A major theme will be that modern molecular biological research has questioned the conventional wisdom that CMV is a slow-growing virus, which only damages a few individuals. I will first review details of the genetic constitution of the virus, emphasizing that wild strains contain many genes which are missing from their laboratory-adapted cousins. I will then review the diseases associated with CMV, not just the end-organ diseases of pneumonitis/retinitis, etc., but the so-called indirect effects, including graft rejection, secondary microbial infections and accelerated atherosclerosis. The urgent need for safe and potent antiviral drugs to prevent these diseases will be considered in two ways: first, the failure of the conventional drug discovery approach; and secondly, the opportunities offered by targeting novel gene functions. The controlled clinical trials performed to date will be summarized, together with suggestions about pharmacodynamic evaluations in the future.

Antifungal Agents↗

PubMed2002

Dural arteriovenous fistulae: noninvasive diagnosis with dynamic MR digital subtraction angiography.

MR digital subtraction angiography (DSA) is a new diagnostic tool capable of producing dynamic images of the cerebral circulation with the injection of gadopentetate dimeglumine into a peripheral vein. Previous reports have concentrated on its potential as a noninvasive technique for the study of pial arteriovenous malformations. In this report, we present our early findings with MR DSA in the evaluation of intracranial dural arteriovenous fistulae.

Aged↗

PubMedDate not supplied

Proton MR spectroscopy of polymicrogyria and heterotopia.

BACKGROUND AND PURPOSE: Proton MR spectroscopy of the brain allows noninvasive in vivo assessment of metabolites, which may be useful in understanding the biology of malformations of cortical development. The aim of this study was to determine the MR spectroscopic characteristics of polymicrogyria and heterotopia compared with those of normal frontal lobe white matter. METHODS: We recruited 22 patients with radiographic findings characteristic of polymicrogyria, nine patients with radiographic findings characteristic of heterotopia, and 10 control subjects into the study. The MR imaging technique consisted of high-spatial-resolution axial dual-echo and gradient-echo 3D volume imaging. A single-voxel point-resolved technique (1600/135 [TR/TE]) was used to acquire spectra from the region of neocortical malformation and from frontal lobe white matter in control subjects. The differences in N-acetyl moieties (NA)/creatine (Cr), NA/choline (Cho), and Cho/Cr ratios among patients with heterotopia, those with polymicrogyria, and control subjects were compared by using the Kruskal-Wallis test followed by the Mann-Whitney U (Wilcoxon) test. RESULTS: No statistically significant differences were noted in the NA/Cr, NA/Cho, and Cho/Cr ratios between the polymicrogyria group and controls, the heterotopia group and controls, or the polymicrogyria and heterotopia groups. CONCLUSION: Both heterotopia and polymicrogyria are malformations of cortical development that occur at a relatively late stage of brain development. The neurons and glia in these lesions are mature, and the metabolites appear to be similar to those of normal adult frontal white matter.

Adolescent↗