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Biomedical subjects

Paul D Griffiths

Publications and source records attributed to Paul D Griffiths.

At least 19 recordsLinked to original sources
PubMed2007

The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors.

A lesser-recognized form of human herpesvirus 6 (HHV-6) persistence is integration of the viral genome in a host chromosome and high viral copy numbers in blood or sera are characteristic of this phenomenon. A cross-sectional study was performed to determine the frequency of high HHV-6 viral loads in whole blood (>6 log(10) copies/ml) in a population of blood donors in London, UK. Blood samples from 500 anonymized blood donors were collected from one donation center, DNA extracted, and quantitative realtime PCR used to measure viral load. Four samples (0.8%) were found to have high viral copy numbers of HHV-6 (median 6.7 log(10) copies/ml; range 6.5- 6.9 log(10) copies/ml). Cellular DNA was also quantitated using qRT-PCR for beta-globin. By comparing these two results, we calculated that there were between two and five copies of HHV-6 present per cell in these four donors. The median viral load detected in plasma from the four individuals was 3.8 log(10) copies/ml (range 3.5-4.0 log(10) copies/ml). All samples were HHV-6 variant B. In addition, a retrospective analysis of all diagnostic blood samples performed for HHV-6 in our center showed a prevalence of 2.9% of high viral loads characteristic of integration. In conclusion, high viral copy numbers of HHV-6, representing a population of viral integration, is detected in 0.8% of UK blood donors. The presence of high HHV-6 viral loads in healthy normal individuals reiterates the need to consider the confounding effect of HHV-6 viral integration in any laboratory diagnosis of HHV-6 infection.

Blood Donors↗
PubMed2006

A multicenter, site-independent, blinded study to compare the diagnostic accuracy of contrast-enhanced magnetic resonance angiography using 1.0M gadobutrol (Gadovist) to intraarterial digital subtraction angiography in body arteries.

PURPOSE: Prospective evaluation of diagnostic accuracy of single field-of-view contrast-enhanced MR Angiography (ceMRA) with 1.0M gadobutrol compared to intraarterial DSA in body arteries. MATERIALS AND METHODS: In an European multicenter study 179 patients underwent ceMRA and DSA. For each indication five prospectively defined vessel segments were evaluated by local investigators onsite and by three site-independent blinded readers (BR) independently. RESULTS: The agreement between ceMRA and DSA diagnosis was statistically significant in the onsite (96.6%) and blinded reader (86.6-90.2%) evaluation. Sensitivity, specificity, accuracy, positive (PPV) and negative predictive values (NPV) for detection of relevant stenosis (>50%) were calculated for the right and left internal carotid arteries, and common and external iliac arteries: Sensitivity was 95-98% (onsite) and 76-96% (BR), specificity 94-96% (onsite) and 86-94% (BR), accuracy 96% (onsite) and 87-93% (BR), NPV 98-99% (onsite) and 84-98% (BR), and PPV 79-93% (onsite) and 44-91% (BR), respectively. CONCLUSION: CeMRA of body arteries using 1.0M gadobutrol provides diagnostic information comparable to intraarterial DSA.

Adult↗
PubMed2006

Assessment of blood supply to intracranial pathologies in children using MR digital subtraction angiography.

BACKGROUND: MR digital subtraction angiography (MR-DSA) is a contrast-enhanced MR angiographic sequence that enables time-resolved evaluation of the cerebral circulation. OBJECTIVE: We describe the feasibility and technical success of our attempts at MR-DSA for the assessment of intracranial pathology in children. MATERIALS AND METHODS: We performed MR-DSA in 15 children (age range 5 days to 16 years) referred for MR imaging because of known or suspected intracranial pathology that required a dynamic assessment of the cerebral vasculature. MR-DSA consisted of a thick (6-10 mm) slice-selective RF-spoiled fast gradient-echo sequence (RF-FAST) acquired before and during passage of an intravenously administered bolus of Gd-DTPA. The images were subtracted and viewed as a cine loop. RESULTS: MR-DSA was performed successfully in all patients. High-flow lesions were shown in four patients; these included vein of Galen aneurysmal malformation, dural fistula, and two partially treated arteriovenous malformations (AVMs). Low-flow lesions were seen in three patients, all of which were tumours. Normal flow was confirmed in eight patients including two with successfully treated AVMs, and in three patients with cavernomas. CONCLUSION: Our early experience suggests that MR-DSA is a realistic, non-invasive alternative to catheter angiography in certain clinical settings.

Adolescent↗
PubMed2006

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis.

Human cytomegalovirus can cause a diverse range of diseases in different immunocompromised hosts. The pathogenic mechanisms underlying these diseases have not been fully elucidated, though the maximal viral load during infection is strongly correlated with the disease. However, concentrating on single viral load measures during infection ignores valuable information contained during the entire replication history up to the onset of disease. We use a statistical model that allows all viral load data sampled during infection to be analysed, and have applied it to four immunocompromised groups exhibiting five distinct cytomegalovirus-related diseases. The results show that for all diseases, peaks in viral load contribute less to disease progression than phases of low virus load with equal amount of viral turnover. The model accurately predicted the time of disease onset for fever, gastrointestinal disease and pneumonitis but not for hepatitis and retinitis, implying that other factors may be involved in the pathology of these diseases.

Cytomegalovirus↗
PubMed2006

Imaging the fetal spine using in utero MR: diagnostic accuracy and impact on management.

BACKGROUND: In-utero MR imaging (iuMR) has entered the clinical arena during the last decade. It is used mainly for imaging fetal brain abnormalities. OBJECTIVE: To report our experience of imaging the fetal spine and spinal cord in fetuses with known or suspected abnormalities diagnosed on US imaging. MATERIALS AND METHODS: Prospective imaging and retrospective analysis of the possible impact on management of 50 consecutive fetuses with spinal abnormalities detected by antenatal US imaging. RESULTS: In 40 (80%) of 50 fetuses, iuMR and US imaging were in complete agreement. In the other 10 fetuses (20%), iuMR provided additional information or changed the diagnosis, including 8 fetuses where the iuMR could find no abnormality and was found to be correct by later follow-up. CONCLUSION: IuMR is useful in fetuses with a suspected spinal abnormality. The clinical impact of iuMR may be numerically less than with brain abnormalities, but is still sufficient to warrant its use, especially if there is any uncertainty about the US imaging, and particularly as a relatively high proportion of diagnoses on US imaging are false-positives.

Female↗
PubMed2006

Antivirals in the transplant setting.

Over the past quarter of a century, antiviral drugs have moved from an experimental adventure in transplant patients to a situation where they are used routinely to prevent diseases caused by several viruses. Furthermore, they have significantly reduced several medical complications of transplantation, such as graft rejection, thereby implicating viruses as components of their pathogenesis. By controlling these major complication, the development of these antiviral drugs and their prodrugs, has therefore greatly facilitated the clinical expansion of transplantation, allowing life saving procedures to be offered to more patients who could potentially benefit. This article will briefly summaries which viruses are important following transplantation and outline the evidence-base from randomized controlled clinical trails for the deployment of antiviral drugs to prevent viral diseases.

Antiviral Agents↗
PubMed2006

Simultaneous parallel inclined readout image technique.

Sensitivity-encoded phase undersampling has been combined with simultaneous slice excitation to produce a parallel MRI method with a high volumetric acquisition acceleration factor without the need for auxiliary stepped field coils. Dual-slice excitation was produced by modulating both spin and gradient echo sequences at +/-6 kHz. Frequency aliasing of simultaneously excited slices was prevented by using an additional gradient applied along the slice axis during data acquisition. Data were acquired using a four-channel receiver array and x4 sensitivity encoding on a 1.5 T MR system. The simultaneous parallel inclined readout image technique has been successfully demonstrated in both phantoms and volunteers. A multiplicative image acquisition acceleration factor of up to x8 was achieved. Image SNR and resolution was dependent on the ratio of the readout gradient to the additional slice gradient. A ratio of approximately 2:1 produced acceptable image quality. Use of RF pulses with additional excitation bands should enable the technique to be extended to volumetric acquisition acceleration factors in the range of x16-24 without the SNR limitations of pure partially parallel phase reduction methods.

Algorithms↗
PubMed2006

Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis.

We identified a stem cell donor with chromosomally integrated human herpesvirus (HHV)-6 and monitored the recipient for HHV-6 after transplantation. The appearance and subsequent increase in HHV-6 load paralleled engraftment and an increase in white blood cell count. Fluorescent in situ hybridization analysis showed integrated HHV-6 on chromosome band 17p13.3 in the donor and in the recipient after transplantation but not in the recipient before transplantation. The increase in viral load due to the genetic transmission of integrated HHV-6 could have been misinterpreted as substantial active infection and, thus, led to the administration of toxic antiviral therapy. We suggest that the confounding influence of integration be considered in laboratory investigations associating HHV-6 with disease.

Adult↗
PubMed2006

MR imaging of recent non-traumatic intracranial hemorrhage: early experience at 3 T.

Magnetic resonance imaging (MRI) using 3.0 T scanners in the clinical environment is in its infancy and is only available at a limited number of sites worldwide. There is great interest amongst radiologists about the perceived benefits of clinical imaging at 3.0 T; however, it remains to be seen whether the theoretical advantages will bring real gains. MRI in patients with non-traumatic intracranial hemorrhage (ICH) is difficult, yet, these patients benefit from non-invasive angiography. Conventional catheter angiography (CCA) remains the reference standard for excluding/confirming the presence of intracranial vascular abnormalities, but MR angiography at 3.0 T may offer opportunities for significant changes in patient management. We present our experiences of using 3.0 T MR angiography in 27 patients with acute or early subacute ICH.

Adult↗
PubMed2006

CMV as a cofactor enhancing progression of AIDS.

BACKGROUND: Cytomegalovirus (CMV) has been proposed as a cofactor driving HIV pathogenicity since the late 1980s. Potential mechanisms which CMV could use as a cofactor have been described in vitro and potential criteria for assessing cofactor activity in vivo have been proposed. OBJECTIVE: To determine if recent publications have added new information to these in vitro or in vivo studies since the author last reviewed this subject in 1998. STUDY DESIGN: Literature survey prior to presenting an overview lecture. RESULTS: No new in vitro mechanisms have been described though several clinical cohort studies are consistent with the possibility that active CMV infection can act as a cofactor. One study published in 1999 showed that mortality in AIDS patients was driven more by CMV viral load than HIV viral load. Although highly active antiretroviral therapy (HAART) has now greatly controlled end organ disease caused by CMV, a recent study showed that CMV viraemia was still strongly associated with death in AIDS patients. CONCLUSIONS: (1) CMV remains important in the era of HAART. (2) CMV has been underestimated as an important cofactor since the beginning of the AIDS epidemic.

AIDS-Related Opportunistic Infections↗
PubMed2006

Effects of creatine supplementation on cerebral white matter in competitive sportsmen.

OBJECTIVES: To determine the neurobiochemical sequelae of oral creatine monohydrate supplementation in active athletes. DESIGN/PARTICIPANTS: Eighteen sportsmen underwent single-voxel proton magnetic resonance spectroscopy of the deep frontal cerebral white matter before and after 5 days of oral ingestion: 12 of 18 swallowed 4 x 5 g creatine monohydrate per day, and the remaining swallowed a placebo. MAIN OUTCOME MEASUREMENTS: Creatine, choline, and N-acetyl spectral resonances were evaluated at both long (135 ms) and short (20 ms) echo times. RESULTS: A mixed-design factorial ANOVA demonstrated no interaction over time in any of the measures (P at least 0.081). CONCLUSIONS: The results suggest that, for the given dosage regimen, ingested creatine augmentation does not alter the magnetic resonance visible creatine pool in the deep frontal cerebral white matter of young active sportsmen.

Administration, Oral↗
PubMed2006

Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles.

Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal integration had HHV-6 and beta-globin DNA quantified in various samples by PCR. The mean HHV-6 DNA concentration (log(10) copies/milliliter) in blood was 7.0 (>/=1 HHV-6 DNA copies/leukocyte), and in serum it was 5.3 (>/=1 HHV-6 DNA copies/lysed cell). The mean HHV-6 DNA load (log(10) copies)/hair follicle was 4.2 (>/=1 copies/hair follicle cell), demonstrating that viral integration is not confined to blood cells. The characteristically high HHV-6 DNA levels in chromosomal integration may confound laboratory diagnosis of HHV-6 infection and should be given due consideration.

Adult↗
PubMed2006

Dexamethasone and enhancing solitary cerebral mass lesions: alterations in perfusion and blood-tumor barrier kinetics shown by magnetic resonance imaging.

OBJECTIVE: Glucocorticoid analogues are often administered to patients with intracranial space-occupying lesions. Clinical response can be dramatic, but the neurophysiological response is not well documented. This study sought to investigate the blood-lesion barrier, blood-brain barrier, and cerebral perfusion characteristics of patients who have undergone such therapy using magnetic resonance imaging. METHODS: Seventeen patients with intracranial mass-enhancing lesions underwent magnetic resonance imaging before and after 3 days of high-dose dexamethasone therapy. Assessments of blood-lesion barrier and blood-brain barrier integrity were based on a dynamic T1-weighted exogenous contrast technique that yielded the normalized maximal change in contrast uptake (T1-uptake). Perfusion was assessed using a dynamic T2*-weighted exogenous contrast technique to yield relative regional cerebral blood volume and first-moment mean transit time. Comparisons were made in T1-uptake, regional cerebral blood volume, and first-moment mean transit time of both enhancing lesion and contralateral normal-appearing white matter (CNAWM) obtained before and after dexamethasone. RESULTS: Significant reduction in T1-uptake was observed (19% decrease, P < 0.005) within enhancing pathological tissue, whereas no significant alteration was detected in CNAWM. Regional cerebral blood volume was significantly reduced in both enhancing tissue (28% decrease, P < 0.005) and in CNAWM (20% decrease, P < 0.001). Bolus first-moment mean transit time significantly increased (2.0 s prolongation, P < 0.05) in CNAWM, whereas there was no significant change (1.4 s prolongation, P > 0.05) within enhancing tissue. CONCLUSION: Glucocorticoid-analogue therapy not only affects the permeability of the blood-lesion barrier and lesion blood volume but also affects blood flow within normal-appearing contralateral parenchyma. There is a need for controls in steroid therapy in magnetic resonance imaging studies, which involve assessments of cerebrovascular function.

Adult↗
PubMed2006

Cerebral perfusion abnormalities in children with Sturge-Weber syndrome shown by dynamic contrast bolus magnetic resonance perfusion imaging.

OBJECTIVE: Sturge-Weber syndrome is characterized by leptomeningeal angiomatosis and a facial naevus that is usually unilateral. Magnetic resonance imaging is the cornerstone of confirming the disease and judging the extent of the abnormalities. It has been shown, however, that brain perfusion abnormalities on nuclear medicine imaging often are more extensive than the abnormal leptomeningeal enhancement on magnetic resonance. In this article, we assess the utility of magnetic resonance perfusion in demonstrating perfusion abnormalities in pediatric cases of Sturge-Weber syndrome. METHODS: Magnetic resonance perfusion studies were performed on 7 consecutive children who presented to our department with clinically suspected Sturge-Weber syndrome. The extent of time to peak abnormality on dynamic gadolinium bolus magnetic resonance perfusion imaging was compared with the extent of leptomeningeal enhancement and the presence of venous abnormalities. RESULTS: Good magnetic resonance perfusion data were obtained in all 7 cases. Perfusion abnormalities were closely anatomically related to meningeal enhancement on postcontrast T1-weighted imaging. However, perfusion abnormalities were found consistently in the vicinity of developmental venous anomalies that were present in 4 of 7 cases. In 1 child, there was a perfusion deficit in the cerebellar lobe contralateral to the leptomeningeal angiomatosis, consistent with crossed cerebellar diaschisis. CONCLUSIONS: Magnetic resonance perfusion is a sensitive indicator of perfusion abnormalities in Sturge-Weber syndrome and can be performed easily at the same time as the diagnostic scan. Magnetic resonance perfusion imaging therefore is useful in the assessment of this disease. This approach has the extra advantage of correlating the perfusion abnormalities with the high-resolution imaging that is provided from magnetic resonance imaging.

Adolescent↗
PubMed2006

Early involvement of the spinal cord in diabetic peripheral neuropathy.

OBJECTIVE: The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN. RESEARCH DESIGN AND METHODS: Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3. RESULTS: Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1-70.9] in diabetic subjects without DPN. Those with subclinical (62.4 mm [59.5-65.3]) and clinically detectable DPN (57.2 mm [54.9-59.6]) had lower mean SCAIs compared with subjects with no DPN (P = 0.03 and P < 0.001, respectively). No significant difference was found between diabetic subjects without DPN and nondiabetic control subjects (69.2 mm [66.3-72.0], P = 0.47). Mean SCAIs in subjects with HSMN type 1A (71.07 mm [65.3-76.9]) were not significantly different from those for nondiabetic control subjects and diabetic subjects without DPN. Among diabetic subjects, SCAI was significantly related to sural sensory conduction velocities and the Neuropathy Composite and Symptom Scores. CONCLUSIONS: Spinal cord involvement occurs early in DPN. There is also a significant relation between reduction in SCAI and neurophysiological assessments of DPN.

Adult↗
PubMed2005

Measurements and modeling of long range 3He diffusion in the lung using a "slice-washout" method.

In healthy lung tissue, pulsed-gradient-spin-echo (PGSE) methods reveal apparent diffusion coefficients (ADC) of the order 0.20 cm2 s(-1); for diffusion times of approximately 2 ms. For these short diffusion times the ADC is only sensitive to structures approximately (2Dt)1/2 approximately 0.6mm in size. Recent work, using magnetic tagging of the longitudinal magnetization has revealed much smaller ADC values for longer length scales. In this work, the in vivo ADC from within the air-spaces, was measured using a new technique. The signal from a series of images was analyzed from a slice that was repeatedly imaged. Diffusion tends to "top-up" the non-renewable polarization within the slice, which leads to a non-exponential decay in image signal. Image data were compared to 1D finite-difference simulations of diffusion to calculate a long range ADC value. The results yield values of the order 0.034 cm2 s(-1), which are nearly an order of magnitude smaller than those reported by PGSE measurements at shorter diffusion times.

Algorithms↗