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Biomedical subjects

P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 163 records · Page 9Linked to original sources
PubMed1996

Incidental intracranial vascular pathology in patients investigated for carotid stenosis.

The assessment of cervical and cranial carotid arteries for atherosclerotic disease is the second commonest referral for angiography in our neuroradiological department; in 1993 this accounted for approximately 17% of the total cases. This is due to the resurgence of interest in endarterectomy for severe carotid stenosis. Although the degree of stenosis can usually be assessed adequately by duplex Doppler ultrasonography, angiography is still recommended as a preoperative examination. The intracranial vessels are visualised, which we consider important when planning vascular surgery. We present a prospective study of 100 patients referred for angiographic assessment of carotid stenosis. As well as giving information about the carotid bifurcation, angiography showed 9 patients to have aneurysms, 2 arteriovenous malformations and 15 severe intracranial atherosclerosis. We consider these "incidental" findings important for future management and highlight the need for thorough assessment of the intracranial vessels in these patients by angiography.

Adult↗
PubMed1996

Summary of the International Consensus Symposium on Advances in the Diagnosis, Treatment and Prophylaxis and Cytomegalovirus Infection.

CMV infection and CMV disease can be difficult to differentiate and the diagnosis is usually based on a compatible clinical picture and the results of a diagnostic test for CMV. The only exception to this rule is in HIV-infected patients where fundoscopy is sufficient to diagnose CMV retinitis. Of the current diagnostic tests, qualitative and quantitative PCR, branched DNA and Hybrid Capture, are the most promising. The pp65 antigenemia assay has the disadvantage of being more labor-intensive than the DNA based tests. Preliminary data show that a positive qualitative PCR in a HIV-infected patient has a predictive value for the development of CMV retinitis. However, of the patients positive by qualitative PCR, those with high viral loads in quantitative PCR were at the greatest risk of CMV disease. This might make it possible to identify with great certainty the patients who will go on to develop CMV retinitis, thereby decreasing the number of patients eligible for preemptive or prophylactic therapy and increasing the cost-benefit of this therapeutic measure. Quantitative test might also be useful in monitoring response to therapy, but randomized trials comparing the test are needed. Prophylactic antiviral agents should not be used in seronegative transplant recipients receiving organs from seronegative donors. In high-risk transplant recipients, ganciclovir should be used. CMV vaccines are useful for the protection of babies from CMV seronegative mothers against congenital CMV disease. It also may be useful in seronegative transplant recipients receiving a seropositive donor organ, although the benefit of chemo prophylaxis may surpass that of vaccine. HIV-infected patients with CMV retinitis who relapse under either ganciclovir or foscarnet benefit from subsequent combination therapy, rather than switching to the other drug. However, the cost is high in terms of quality of life. Intravitreal therapy for CMV retinitis is very efficacious, suggesting that drug delivery is a problem in systemic therapy. However, intravitreal therapy does not protect against the development of CMV retinitis in the contralateral eye or from CMV disease elsewhere. Therefore, systemic therapy should be added. CMV disease of the CNS should be diagnosed early and treated agressively, possible with combination therapy. A diagnosis of CMV disease should be based on a compatible clinical picture and the demonstration of CMV in CSF by DNA or antigen assays which are more sensitive than culture.

Animals↗
PubMed1996

Arthrogryposis multiplex congenita and bilateral parietal polymicrogyria in association with the intrauterine death of a twin.

A case of neurogenic arthrogryposis multiplex congenita (AMC) with associated neuronal migration abnormalities is described. A child with neurogenic AMC and developmental delay presented with late onset of seizures. The first trimester of the mother's pregnancy was marked by an episode of gastro-enteritis and the intrauterine death of a twin fetus. Computer tomography (CT) and magnetic resonance (MR) imaging demonstrated abnormal neuronal migration consisting of bilateral parietal polymicrogyria, and an isolated grey matter heterotopia.

Age of Onset↗
PubMed1996

Sturge-Weber syndrome revisited: the role of neuroradiology.

In this article I review the typical clinical and neuroradiological features of Sturge-Weber syndrome and introduce some of the recently described findings demonstrated by magnetic resonance imaging and perfusion-based single photon emission computed tomography. The article is concluded by a discussion into the most efficient way of imaging children with Sturge-Weber syndrome.

Brain↗
PubMed1996

Measurement of human herpesvirus 7 load in peripheral blood and saliva of healthy subjects by quantitative polymerase chain reaction.

Qualitative and competitive-quantitative nested polymerase chain reaction (PCR) assays were developed for human herpesvirus 7 (HHV-7). These assays amplify a DNA sequence encoding part of the HHV-7 homologue of the human herpesvirus 6 (HHV-6) U42 gene. The PCR assays were used to analyze peripheral blood DNA (pbDNA) and saliva from 24 healthy volunteers. The prevalence of HHV-7 in saliva was 96%, with a median virus load of 1.1 x 10(6) copies/mL. Longitudinal analysis revealed sustained virus load, suggesting continued active viral replication. Analysis of 1 microgram of pbDNA showed the prevalence of HHV-7 to be 83%, with a median virus load of 40 copies (267 copies/10(6) cells). Analysis of sequential pbDNA samples showed individuals to have stable levels of HHV-7 virus load. These data demonstrate persistence of HHV-7 at two distinct sites and provide baseline data allowing comparisons with HHV-7 load in immunocompromised patients.

Base Sequence↗
PubMed1996

Herpesviruses and AIDS.

Herpesviruses and retroviruses are distinct taxonomically, yet have the potential for multiple bidirectional interactions. In vitro, these interactions have largely been studied in terms of herpesvirus up-regulation of HIV genome expression and/or transmissibility. This can be demonstrated in vitro through experiments showing transactivation, CD4 up-regulation, Fc receptor induction, pseudotype formation, cytokine production, and antigen presentation. In addition, once HIV has induced immunosuppression several herpesviruses can reactivate, and so cause disease in their own right. The in-vivo correlates of these phenomena are difficult to study in humans but evidence is reviewed to support the concept that herpesviruses may be activating HIV, so that potential clinical benefit could be obtained through the use of antiviral drugs active against herpesviruses. Whether the clinical benefits seen in particular trials could be ascribed to inhibition of herpesvirus disease, or to herpesvirus infection driving HIV pathogenesis, remains a controversial area.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Quantification of human herpesvirus 6 in immunocompetent persons and post-mortem tissues from AIDS patients by PCR.

A quantitative competitive PCR assay for human herpesvirus 6 (HHV-6) was developed. Firstly, viral burden was determined in the blood of 25 healthy persons. Using 1 microgram of DNA, the prevalence of HHV-6 was 36% (9/25). Eight persons had viral loads of < or = 32 HHV-6 genomes/microgram DNA. The viral burden in the ninth individual was 1.2 x 10(6) HHV-6 genome copies/microgram DNA, which remained constant over a period of 10 months. This demonstrates the persistence of a high HHV-6 load in the absence of apparent disease. Secondly, HHV-6 burden was determined in 100 post-mortem tissues from seven AIDS patients and three controls. For all tissues combined, there was a statistically significant higher median viral load in AIDS patients (56 copies/microgram DNA, range 0-43321) compared to controls (10 copies/microgram DNA, range 0-423) (P = 0.04). The precision and reproducibility of this assay will allow hypotheses concerning the pathogenic potential of HHV-6 to be tested quantitatively.

AIDS-Related Opportunistic Infections↗
PubMed1996

Abnormal ocular enhancement in Sturge-Weber syndrome: correlation of ocular MR and CT findings with clinical and intracranial imaging findings.

PURPOSE: To estimate the prevalence of abnormal ocular enhancement in children with Sturge-Weber syndrome as detected with MR imaging and CT and to correlate this with the clinical, fundoscopic, and intracranial imaging findings. METHODS: Fifteen children, 4 years old or younger, with Sturge-Weber syndrome were examined with enhanced CT and MR imaging. Eleven children had unilateral intracranial involvement and 4 had bilateral involvement, for a total of 19 abnormal hemispheres and related orbits. The presence of ocular enhancement was compared with the fundoscopic findings independently. Ocular enhancement was correlated with the extent of leptomeningeal disease, the severity of the cutaneous lesion, and the presence of glaucoma by the calculation of likelihood ratios and 95% confidence limits. RESULTS: Seven of the 15 patients had abnormal ocular enhancement, which was present in 10 (53%) of the eyes associated with the 19 abnormal hemispheres. MR imaging showed choroidal hemangioma in 7 of 8 patients in whom hemangiomas were shown at fundoscopy. The likelihood of ocular enhancement was increased with the presence of bilateral disease, extensive facial nevi, and glaucoma; there was no significant correlation with the extent of hemispheric involvement. CONCLUSION: Both enhanced MR imaging and CT can show diffuse choroidal hemangioma in patients with Sturge-Weber syndrome. However, MR imaging is more sensitive and is recommended to aid in the detection of abnormalities with preventable late complications.

Brain↗
PubMed1996

Choroid plexus size in young children with Sturge-Weber syndrome.

PURPOSE: To assess the size of the choroid plexus in young children with unilateral and bilateral Sturge-Weber syndrome. METHODS: Subjects included 15 children 4 years old or younger with Sturge-Weber syndrome. Eleven cases were unilateral and four were bilateral. Unilateral or bilateral involvement was determined by the distribution of abnormal leptomeningeal enhancement on MR images. The diameters of the choroid plexus were measured on contrast-enhanced axial MR images. The choroid plexus of the affected and unaffected sides in these cases were compared with those of 15 age-matched children without Sturge-Weber syndrome who were being examined for seizures. RESULTS: Our results show a wide variation in the size of the choroid plexus in children with Sturge-Weber syndrome; however, plexus associated with a hemisphere affected by Sturge-Weber syndrome were significantly larger than those on the unaffected side and in the age-matched control group. The size of the choroid plexus was positively correlated with the extent of leptomeningeal involvement as demonstrated by abnormal contrast enhancement. CONCLUSION: The choroid plexus is enlarged early in the course of Sturge-Weber syndrome in both unilateral and bilateral cases. There is a positive correlation between choroid plexus size and extent of leptomeningeal involvement in children with Sturge-Weber syndrome.

Child, Preschool↗
PubMed1996

Lessons from the natural history of cytomegalovirus.

BACKGROUND: More than 90% of patients with HIV have been infected at some time with cytomegalovirus (CMV) and up to 40% of those with advanced HIV will develop CMV disease. The incidence of CMV disease is increasing but the prognosis for the patient remains poor. MONITORING FOR CMV: It is therefore important to monitor patients with low CD4+ counts in order to identify those most at risk of developing CMV disease and to treat them before the disease becomes established. Polymerase chain reaction (PCR) is probably the most effective and sensitive method of detecting CMV and a positive result is predictive for development of CMV disease; more than 80% of patients with CMV retinitis are CMV PCR-positive at the time of diagnosis. PCR can also detect the presence of CMV up to 14 months before the development of retinitis. TREATMENT OF CMV RETINITIS: In patients with detectable CMV, but no evidence of active infection, pre-emptive treatment with ganciclovir or valaciclovir has been shown to reduce the risk of developing retinitis in these high-risk patients. Such oral therapy, which is generally better tolerated than intravenous therapy and results in a better quality of life for the patient, is likely to be more effective at this stage whilst viral loads are low. CONCLUSIONS: CMV PCR can be used to prospectively monitor patients in order to identify those most at risk of developing CMV retinitis. If CMV infection is diagnosed early, while viral loads are still low, pre-emptive oral therapy can be instituted which will reduce the chances of developing retinitis in those patients most at risk.

AIDS-Related Opportunistic Infections↗
PubMed1996

Herpesviruses and AIDS.

It is well recognized clinically that herpesviruses can cause disease in AIDS patients once human immunodeficiency virus (HIV) has precipitated marked immunosuppression. However, in addition to this opportunistic relationship, there is evidence to suggest that herpesviruses could increase the pathogenicity of HIV by acting as cofactors. Experiments in vitro have shown that several herpesviruses can activate HIV gene expression or alter the cellular tropism of HIV through a variety of mechanisms (antigen presentation, cytokine release, pseudotype formation, CD4 cell surface upregulation, Fc receptor formation, transactivation). Studies of human autopsy material have shown that some herpesviruses (particularly cytomegalovirus, human herpes virus 6 and herpes simplex virus) are found frequently in AIDS patients. If such herpesviruses act as cofactors in vivo, then their inhibition by aciclovir could explain why a survival benefit has been reported from the use of this drug in two double-blind, placebo-controlled randomized trials.

AIDS-Related Opportunistic Infections↗
PubMed1995

Use of the polymerase chain reaction to detect genomes of human immunodeficiency virus and cytomegalovirus in post-mortem tissues.

The polymerase chain reaction (PCR) was used to amplify a 149 base-pair region of the cytomegalovirus (CMV) genome and a 551 base-pair region of the HIV-1 proviral long terminal repeat (LTR) present in DNA extracted from post-mortem tissue. Multiple tissues (n = 116) obtained from 16 patients which were subjected to PCR were also subjected to cell culture and histopathological analyses. One hundred and seven samples (92%) contained CMV DNA and 66/116 (57%) contained HIV proviral DNA at a level of > or = 10 genomes. Both viruses were detected in 60/116 (51.7%) of samples, with co-infection most frequent in the lung (69%). Cell culture for CMV detected 9.3% of the PCR-positive samples, whilst histology identified CMV inclusions in 15.9% of samples, all of which were CMV PCR-positive. CMV was most frequently detected in adrenal and lung tissues by histology. These results show that co-infection with CMV and HIV is a common occurrence in organs from AIDS patients and provide further evidence for a role of cytomegalovirus in the pathogenesis of AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1995

Cerebrotendinous xanthomatosis in two sisters: case reports and MR imaging.

Cerebrotendinous xanthomatosis is a rare inherited disorder of bile acid metabolism producing xanthomata and severe, progressive neurological deficits. In spite of the rarity of the condition it is important because it is treatable: the neurological deterioration can be halted and in some cases reversed.

Adult↗
PubMed1995

The effect of CMV infection on progression of human immunodeficiency virus disease is a cohort of haemophilic men followed for up to 13 years from seroconversion.

The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years follow-up. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0.05 x 10(9)/l were 2.28, 2.42 and 2.34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1.89, 1.82 and 1.93 respectively and were marginally non-significant (P = 0.05, 0.08 and 0.08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a 'co-factor' effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Viral complications after transplantation.

All hospital patients are at risk of acquiring infections from visitors or staff members or by nosocomial transmission. Transplant patients have additional routes of acquisition which together represent the major source of infection. These are: reactivation of latent virus; transmission with the donor organ; and transmission by blood. A wide variety of viruses have been implicated, with the common feature that they establish either chronic or latent infection in the donor or recipient. The aim of this paper is to review the natural history, clinical features, diagnosis, prevention and treatment of each of these viral infections. A basic principle will be that the presence of specific antibodies in a donor or recipient before undergoing transplantation is a marker of latent virus within that individual. After transplantation, patients have impaired immune responses, thereby rendering serology unreliable for diagnostic purposes. Instead, methods which detect the virus directly in clinical material should be used.

Adenoviridae Infections↗