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P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 91 records · Page 5Linked to original sources
PubMed2001

In vivo measurement of cerebral blood flow: a review of methods and applications.

This article reviews the concepts of cerebral blood flow for the clinician involved in the management of patients with carotid stenosis and/or ischaemic stroke. Methods of assessing cerebral blood flow in vivo using nuclear medicine, magnetic resonance and X-ray computed tomography are described. Applications of magnetic resonance and X-ray computed tomographic methods are reviewed and illustrated by examples from the authors' radiological practice.

Blood Flow Velocity↗
PubMed2001

Multimodality MR imaging depiction of hemodynamic changes and cerebral ischemia in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a common and serious neurologic emergent condition. We tested the hypothesis that multimodality MR imaging depicts changes in cerebral blood flow SAH, before any surgical or endovascular intervention, and that the frequency of these changes increases with time after ictus. METHODS: We prospectively examined 37 patients with suspected SAH and three with symptoms of acute stroke but who subsequently had SAH. Routine CT and multimodality MR imaging were performed within 18 h of presentation. Standard MR imaging, diffusion-weighted MR imaging, time-of-flight MR angiography, and dynamic first-pass gadolinium-enhanced MR perfusion imaging were performed. Images were reviewed for abnormalities in cerebral blood flow, ischemia, and infarction. Nine patients did not have SAH at CT and CSF investigations. Of 31 patients with proved SAH, 13 were examined during the acute stage (within 4 d of ictus) and 18, during the subacute stage (4-14 d after ictus). RESULTS: MR imaging showed alteration in cerebral blood flow parameters in 16 of 31 patients before surgery or endovascular treatment. The frequency of blood flow changes and associated complications increased with worsening clinical grade and increasing time after ictus. CONCLUSION: Multimodality MR imaging provides information not available from CT in patients with SAH. MR imaging shows oligemic and ischemic areas in SAH before surgery or endovascular treatment. MR imaging is a simple noninvasive method of assessing cerebral blood flow and its complications in SAH. It can be performed in a clinical environment.

Adult↗
PubMed2001

Brain MR perfusion imaging in humans.

PURPOSE: To evaluate any possible advantages of high-concentration gadolinium chelates in the human brain thin-slice MR. MATERIAL AND METHODS: Thirty-six patients were allocated into six groups. Three groups had perfusion imaging performed using 7-mm-thick slices and the other three groups had 4-mm-thick slices. One group who had 7-mm slices and one group of 4-mm slices had 0.5 M gadolinium (20 ml) whilst other groups received the high-concentration gadolinium (1.0 M: 10 ml and 20 ml). The time-intensity curves were analysed for maximum signal reduction and signal-to-noise measurements. RESULTS: Twenty ml of the 1.0-M agent produced significantly increased maximum signal change and improvement in signal-to-noise when compared to 20 ml of 0.5 M. There was no significant difference between the maximum signal change when 20 ml of 0.5 M and 10 ml of 1.0 M agents were compared. There was no significant difference between the maximum signal changes when 7-mm and 4-mm slice thickness using the same dosing regimens. CONCLUSION: Four-mm slice thickness perfusion imaging can be performed with high-concentration gadolinium in the human brain and we discuss the advantages of this.

Adolescent↗
PubMed2000

Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy.

Cytomegalovirus (CMV) replicates rapidly in its human host with a doubling time of approximately 1 day. Using simple mathematical models we show that the efficacy of the anti-CMV drug ganciclovir (GCV) against wild-type strains is 91.5% [95% confidence interval (CI) 89-94%] when given i.v. (5 mg/kg twice a day) but only 46.5% (95% CI 45-47.5%) when given orally (1 g three times a day) whereas the corresponding figures for a typical GCV-resistant virus are 62% (95% CI 57-66%) and 35% (95% CI 33-37%), respectively. During prolonged periods of GCV therapy we show that the apparent sudden appearance of GCV resistance is explained by the combination of two exponentially increasing populations (wild type and mutant) at doses of GCV that do not completely inhibit CMV replication. Cell culture methods to assess CMV drug resistance in vivo will underestimate its prevalence because of the fitness loss of resistant virus in the absence of therapy. The parameters determined from these models then were used to predict the likely viral load and resistance patterns in patients on prolonged therapy with GCV. The modeled and experimental data showed excellent agreement over extended time periods (up to 270 days of therapy) and provide a framework to predict the virologic course of patients at therapeutic initiation.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy.

OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of cytomegalovirus (CMV) retinitis. DESIGN AND PARTICIPANTS: Retrospective analysis of 103 consecutive patients diagnosed with CMV retinitis between 1990 and 1998. SETTING: Specialist HIV medicine department of a London hospital. MAIN OUTCOME MEASURES: Incidence of CMV retinitis, time to death following diagnosis, episodes of progression, incidence of inflammatory complications. The date of first use of HAART was January 1995. Data were censored on 30 June 1998. RESULTS: The incidence of CMV retinitis has declined dramatically following the introduction of HAART. Survival following CMV retinitis increased from a median of 0.65 years prior to 1995 to a median of 1.07 years after this date (P = 0.004). In multivariate analyses HAART was independently associated with improved survival (P = 0.02) and the association with year of diagnosis was no longer significant, suggesting that this effect is predominantly due to HAART. None of the patients receiving HAART experienced progression after 6 months of treatment. Complications of retinitis such as retinal detachment, uveitis and optic atrophy occurred in 39% of patients. The rare inflammatory complications of vitritis and cystoid macular oedema occurred only in recipients of HAART. CONCLUSIONS: The introduction of HAART has had a major impact on the natural history of CMV retinitis with improved survival time and decreased risk of progression following diagnosis. However, immune reconstitution may be associated with inflammatory complications which can result in significant visual loss in the absence of active CMV disease.

AIDS-Related Opportunistic Infections↗
PubMed2000

Prospective study of human betaherpesviruses after renal transplantation: association of human herpesvirus 7 and cytomegalovirus co-infection with cytomegalovirus disease and increased rejection.

BACKGROUND: Human herpesvirus 6 (HHV-6) and HHV-7 are two lymphotropic herpesviruses, which, like cytomegalovirus (CMV), have the potential to be pathogenic in immunocompromised individuals. We have conducted a prospective investigation to compare the natural history of HHV-6 and HHV-7 infection with that of CMV after renal transplantation. METHODS: Polymerase chain reaction was used to identify infections and quantify the viral load of CMV, HHV-6, and HHV-7 in peripheral blood samples from 52 renal transplant recipients. Betaherpesvirus infections were related to defined clinical criteria obtained by detailed examination of the clinical records of each patient for the immediate 120-day posttransplant period. RESULTS: CMV was the most commonly detected virus after transplant (58% of patients), followed by HHV-7 (46%) and HHV-6 (23%). Examining the time to first polymerase chain reaction positivity, HHV-7 infection was detected earlier than CMV (P=0.05). The median maximum CMV viral load was significantly higher than those for HHV-6 (P=0.01) and HHV-7 (P<0.0001) and a trend for HHV-7 viral load to be greater than HHV-6 (P=0.08). Clinicopathological analyses revealed that, in those patients with rejection, HHV-7 was associated with more episodes of rejection (P=0.02). In addition, there was a significant increase in CMV disease occurring in patients with CMV and HHV-7 co-infection compared to those with CMV infection only (P=0.04). CONCLUSIONS: HHV-7 should be further investigated as a possible co-factor in the development of CMV disease in renal transplant patients and may potentially exacerbate graft rejection. No clear pathological role was observed for HHV-6.

Betaherpesvirinae↗
PubMed2000

Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation.

BACKGROUND: Cytomegalovirus (CMV) continues to be a major problem post-transplantation; early markers for predicting patients at risk of CMV disease are needed. Peak CMV load in the blood correlates with CMV disease but frequently occurs too late to provide prognostic information. METHODS: 359 transplant recipients (162 liver, 87 renal, and 110 bone marrow) were prospectively monitored for CMV DNA in the blood with qualitative and quantitative PCR. 3873 samples were analysed. The CMV load in the first PCR-positive sample and the rate of increase in CMV load in blood during the initial phase of replication were assessed as risk factors for CMV disease using logistic regression. FINDINGS: 127 of the 359 patients had CMV DNA in the blood and 49 developed CMV disease. Initial viral load correlated significantly with peak CMV load (R2=0.47, p=<0.001) and with CMV disease (odds ratio 1.82 [95% CI 1.11-2.98; p=0.02; 1.34 [1.07-1.68], p=0.01, and 1.52 [1.13-2.05], p=0.006, per 0.25 log10 increase in viral load for liver, renal, and bone-marrow patients, respectively). The rate of increase in CMV load between the last PCR-negative and first PCR-positive sample was significantly faster in patients with CMV disease (0.33 log10 versus 0.19 log10 genomes/mL daily, p<0.001). In multivariate-regression analyses, both initial CMV load and rate of viral load increase were independent risk factors for CMV disease (1.28 [1.06-1.52], p=0.01, per 0.25 log10 increase in CMV load and 1.52 [1.06-2.17], p=0.02, per 0.1 log10 increase in CMV load/mL daily, respectively). INTERPRETATION: CMV load in the initial phase of active infection and the rate of increase in viral load both correlate with CMV disease in transplant recipients; in combination, they have the potential to identify patients at imminent risk of CMV disease.

Cytomegalovirus↗
PubMed2000

Cytomegalovirus seropositivity and human immunodeficiency virus type 1 RNA levels in individuals with hemophilia.

The effect of cytomegalovirus (CMV) seropositivity on the course of human immunodeficiency virus (HIV) type 1 RNA levels and HIV disease progression was assessed in a cohort of 109 hemophilic men infected with HIV-1 for a median of 12.7 years. There was no evidence of higher HIV RNA levels in the first year after HIV seroconversion (P=. 88) or faster rates of increase over infection (P=.20) in the 59 CMV-seropositive individuals than in the CMV-seronegative individuals. In univariate analyses, CMV seropositivity was associated with significantly faster progression to AIDS and death (relative hazards of 1.58 and 2.22, respectively). These effects were unchanged after adjusting for the RNA level, but they were reduced after adjusting for the CD4 cell count, age at seroconversion, and calendar year of follow-up. Thus, the effect of CMV seropositivity on clinical progression remains significant in this cohort but does not appear to be mediated through an increase in HIV RNA levels.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Infrequency of pulmonary microbial colonisation prior to respiratory disease in HIV-infected individuals.

To determine whether organisms are present in the HIV-infected lung prior to clinical respiratory disease, a cross-sectional bronchoscopic comparative analysis of 39 asymptomatic HIV-positive subjects and 31 healthy controls with 2-year prospective bronchoscopic monitoring of the HIV study group was performed. Pathological examination of bronchoalveolar lavage (BAL) fluid using standard microbiological techniques was undertaken. Organisms were recovered from similar numbers of HIV-positive and control subjects (7 of 39 and 3 of 31) and comprised predominantly scanty growths of bacteria. Five subjects developed respiratory disease during follow-up. Repeat BAL was performed in 11 asymptomatic HIV-positive patients; no relationship was found between the organisms isolated at the two procedures. The findings suggest that the asymptomatic HIV-positive lung is not a frequent site of either microbial colonisation or subclinical infection. This has implications for the understanding of the pathogenesis of HIV-related pulmonary disease.

Adult↗
PubMed2000

Comparison of Doppler ultrasound, magnetic resonance angiographic techniques and catheter angiography in evaluation of carotid stenosis.

AIM: To compare the accuracy of ultrasound and two magnetic resonance (MR) angiographic techniques with catheter angiography in assessing atherosclerosis at the carotid bifurcation. MATERIALS AND METHODS: Forty patients with symptomatic carotid stenosis were studied by Doppler ultrasound, time-of-flight MR angiography, contrast-enhanced MR angiography and conventional catheter angiography. The degree of stenosis found on ultrasound and MR angiography was compared with the results of catheter angiography. Four different assessment methods were conducted for the MR angiographic data. Kappa, sensitivity and specificity (with confidence intervals) values were calculated for the US and MR angiography results compared to catheter angiography. RESULTS: Catheter angiography showed 12 internal carotid artery occlusions (15%), 34 severe (44%), 12 moderate (15%) and 20 mild stenoses (26%), using NASCET criteria. Ultrasound showed 65% sensitivity and 95% specificity in detecting surgically amenable lesions, whilst the MR angiographic techniques had sensitivities varying from 82-100%, and specificities from 95-100%.A moderate kappa value was calculated for the US data, whilst all MR techniques were found to show very good agreement with catheter angiography. CONCLUSION: This data suggests that MR angiography is more accurate than Doppler ultrasound in defining surgical lesions and has comparable accuracy to catheter angiography. The use of contrast-enhanced MR angiography is useful in certain situations but is not essential in all cases.

Aged↗
PubMed2000

Acute neuromedical and neurosurgical admissions. Standard and ultrafast MR imaging of the brain compared with cranial CT.

PURPOSE: To evaluate the role of standard and ultrafast MR brain imaging and compare the information with CT. MATERIAL AND METHODS: This was a prospective study of 114 patients with acute neurological symptoms and signs. CT brain examinations consisted of axial non-enhanced images. MR imaging consisted of standard spin-echo/fast spin-echo sequences and a series of rapid techniques including echoplanar and single shot fast spin-echo sequences. RESULTS: Using standard MR methods, 41% of the patients had all five sequences of good technical quality, while using ultrafast methods 81% of the patients had good technical quality examinations in all five sequences. In 3% of the cases, ischaemic stroke was incorrectly reported on CT. In 24% of the cases, MR gave extra diagnostic information not reported on CT and in a further 8%, one neuroradiologist reported the abnormality in agreement with the MR, whilst the other neuroradiologist reported the CT as normal. In 2 cases, subarachnoid haemorrhage was missed on MR. Subarachnoid haemorrhage was not shown on the ultrafast sequences. CONCLUSION: MR can be used to image acute neurological admissions with a high success rate, particularly using ultrafast methods. In many cases, MR provided extra information of direct clinical relevance not shown on CT.

Acute Disease↗
PubMed2000

Brain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence.

Iron content of the basal ganglia was investigated in 25 patients with idiopathic Parkinson's disease and 14 matched healthy control subjects using a partially refocused interleaved multiple echo sequence on a 1.5 Tesla MRI system. R(2)* (1/T(2)*) and R(2)' (1/T(2)') relaxation rates were higher in the substantia nigra of patients with Parkinson's disease, which indicates that iron content is elevated in this region. R(2)' was lower in the putamen, indicating reduced iron levels; reduction in this region was positively correlated with disease duration. Iron-related oxidative stress may contribute to the neurodegeneration of Parkinson's disease, which may lead to alterations in the iron levels of the striatum. We describe a simple, non-invasive technique for measuring iron content.

Adult↗
PubMed2000

Betaherpesviruses in transplant recipients.

The three betaherpesviruses known to infect humans are cytomegalovirus (CMV) and human herpesviruses 6 and 7 (HHV-6 and -7). All three viruses can infect opportunistically after organ transplantation. CMV causes a variety of end-organ diseases, including pneumonitis, hepatitis and gastrointestinal ulceration. Patients who develop overt CMV disease have significantly higher CMV viral loads than infected patients without evidence of clinical disease. A high CMV viral load largely explains the previously described risk factors for the development of CMV disease, which include donor/recipient serostatus before transplant and viraemia after transplant. CMV also causes some cases of allograft rejection, which can be prevented by antiviral prophylaxis. Application of similar quantitative methods for the study of HHV-6 and -7 have shown that HHV-6 and CMV are significantly and independently associated with biopsy-proven graft rejection after liver transplantation. The full clinicopathological significance of the betaherpesviruses may, thus, be greater than is currently appreciated.

Antiviral Agents↗
PubMed2000

Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7.

BACKGROUND: Cytomegalovirus (CMV) is the prototype member of the beta-herpesvirinae, which can cause multiple organ dysfunction in the immunocompromised host. Human herpesvirus 6 (HHV-6) and HHV-7 are newer members of the beta-herpesvirinae that can cause febrile illness in young children and are also possible pathogens in the immunocompromised patient. AIM: CMV is detected in histopathological sections by visualisation of owl's eye inclusion bodies. The aim of this study was to quantify the relation between CMV, HHV-6, and HHV-7 viral loads and the presence of owl's eye inclusions in histological sections. METHODS: Histopathological examination of postmortem material and recording of owl's eye inclusion bodies were performed. CMV, HHV-6, and HHV-7 were detected by qualitative and quantitative polymerase chain reaction (PCR) from the same postmortem samples. Statistical analysis of the histopathological and PCR results was performed. RESULTS: There was a significant association between the detection of owl's eye inclusion bodies and positive CMV PCR (p < 0.001); the median CMV viral load was significantly higher in samples that were positive for owl's eye inclusions (p < 0.001). No association was found between the presence of owl's eye inclusions and HHV-6 or HHV-7 positivity. CONCLUSION: Histological detection of owl's eye inclusion bodies is an insensitive but highly specific method for detecting CMV organ involvement. Owl's eye inclusion bodies are not associated with HHV-6 or HHV-7 infection.

Cytomegalovirus↗
PubMed2000

Unilateral leptomeningeal enhancement after carotid stent insertion detected by magnetic resonance imaging.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty combined with vascular stenting is currently being assessed in the treatment of patients with symptomatic, severe carotid stenosis. The immediate cerebral hemodynamic effects resulting from stenting are not fully understood. This article describes a novel finding: abnormal leptomeningeal enhancement after stenting shown by MRI. METHODS: Fourteen patients with symptomatic severe carotid bifurcation stenosis underwent MRI within 4 hours before and within 3 hours after attempted carotid stenting. Twelve patients were successfully stented. Part of the MR investigation consisted of the acquisition of T1-weighted images before and after administration of the contrast agent Gd-DTPA, both before and after the procedure. RESULTS: All 12 patients who underwent successful stenting did not have abnormal enhancement of the leptomeninges before stenting but developed unilateral enhancement following intervention but before the second injection of contrast agent. No contrast enhancement was detected in the 2 patients who had the angiographic procedure but were not stented. CONCLUSIONS: These findings suggest that abnormal changes to the leptomeningeal vasculature occur during carotid stenting which are not associated with sudden development of neurological symptoms. The anatomic distribution of the enhancement suggests that it is a consequence of the sudden change in brain hemodynamics secondary to the improvement in carotid flow after stenting.

Aged↗
PubMed1999

Recombinant gp160 as a therapeutic vaccine for HIV-infection: results of a large randomized, controlled trial. European Multinational IMMUNO AIDS Vaccine Study Group.

OBJECTIVES: The primary objective of this study was to expand the safety and immunogenicity database of recombinant gp160 as a therapeutic vaccine in the treatment of HIV-infection. Preliminary efficacy data was also sought. DESIGN: This trial was a randomized, double-blind, placebo-controlled study. Two-hundred and eight volunteers, 96 therapy-naive with CD4 cell count >500x10(6)/l (group A) and 112 with CD4 cell count of 200-500x10(6)/l (group B, 51 out of 112 on treatment with one or two nucleoside analogues), received monthly injections of rgp160 IIIB vaccine or placebo for the first 6 months of the study; booster immunizations with rgp160 MN or placebo were given at times 15, 18, and 21 months. METHODS: Safety and immunogenicity data were obtained and measurements of CD4 cell count, plasma viral RNA, and proviral DNA were performed. Clinical outcome was recorded for the 24 months of study. RESULTS: The vaccine was safe and well tolerated. Despite the induction of new rgp160-specific lymphoproliferative responses and the presence of positive delayed type hypersensitivity skin tests to rgp160 at the end of the 24 month study, no effect on the natural history of HIV infection was detected. Within 24 months, AIDS-defining illnesses had occurred in 19 of the vaccinated volunteers and in 18 of the placebo recipients. Persons with higher plasma viral RNA levels and higher proviral DNA had a more rapid decline in CD4 cell count when compared to persons with lower values. Vaccine did not alter viral RNA or proviral DNA levels. CONCLUSION: There was no clinical benefit to therapeutic immunizations with rgp160, despite the induction of new lymphoproliferative responses.

AIDS Vaccines↗
PubMed1999

The dynamics of human cytomegalovirus replication in vivo.

Cytomegalovirus (CMV) is generally described as a slowly replicating virus. During studies of immunocompromised patients, we observed rapid changes in the quantity of CMV DNA present in serial blood samples by quantitative-competitive polymerase chain reaction commensurate with a doubling time of <2 d. To further investigate the dynamics of replication in vivo, patients in three distinct situations were studied in detail: (a) those receiving intravenous ganciclovir; (b) those in whom ganciclovir-resistant strains appeared during long-term therapy; and (c) those in whom ganciclovir-resistant strains disappeared with alternative drug therapy. In all cases, it was possible to provide accurate estimates of the doubling time of CMV and its half-life of disappearance after antiviral chemotherapy. The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is approximately 1 d when frequent samples are collected. These results show that CMV DNA replication in vivo is a highly dynamic process. We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted. These findings have implications for the potency, dose, and duration of antiviral chemotherapy needed for the effective treatment of this important human pathogen.

Antiviral Agents↗