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P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 145 records · Page 8Linked to original sources
PubMed1998

Transcription of the human cytomegalovirus natural killer decoy gene, UL18, in vitro and in vivo.

Multiplex RT-PCR analysis of human cytomegalovirus (HCMV) replication in human fibroblasts showed transcription of the natural killer (NK) cell decoy gene, UL18, from 72 h onwards. Transcription of glycoprotein B (gpUL55; a late gene) occurred from early time-points and peaked at 24 h post-infection. UL18 mRNA was also detected in the peripheral blood mononuclear cells of organ transplant recipients with HCMV viraemia, especially those with HCMV DNA virus loads greater than 10(5) genomes/ml whole blood. Thus, UL18 is produced via a low abundance transcript late during the infectious cycle at a time coincidental with the increased risk of NK cell lysis as a consequence of class I HLA down-regulation.

Base Sequence↗
PubMed1998

Evaluation of carotid endarterectomy with sequential MR perfusion imaging: a preliminary report.

BACKGROUND AND PURPOSE: Current indications for carotid endarterectomy are determined by balancing the relative risks of surgery with the benefits of reduced risk of subsequent stroke. Our purpose was to use MR perfusion imaging to assess patients being considered for carotid endarterectomy and to monitor sequential changes in MR perfusion characteristics after surgery. In particular, we wished to determine whether this technique could be used to detect changes that might be related to post-carotid endarterectomy hyperemia. METHODS: We used a single-section gradient-recalled echo sequence to investigate 14 patients being examined before possible surgery for carotid artery disease. In the 12 patients in whom carotid endarterectomy was performed, sequential studies were performed 3 to 5 days after surgery and at 3 months. Analysis of bolus-arrival-time (BAT) images was performed. RESULTS: Significant delays in preoperative BAT images of 0.89 seconds (range, 0.05 to 3.22 seconds) were apparent between hemispheres. Excluding the two patients with contralateral internal carotid artery (ICA) occlusion, early arrival, possibly indicating postoperative hyperemia, was seen in five patients immediately after carotid endarterectomy but resolved within 3 to 5 months after surgery. CONCLUSION: MR perfusion imaging shows differences in BAT between hemispheres in patients with ICA stenosis. Changes in perfusion characteristics after carotid endarterectomy are complex, and early BAT on the operative side can occur soon after endarterectomy in over half those patients without an occluded contralateral vessel. The significance of these findings with regard to patient outcome and risk of postoperative hyperemia requires further investigation.

Aged↗
PubMed1997

Association of tuberous sclerosis of temporal lobes with autism and atypical autism.

BACKGROUND: Tuberous sclerosis (TS) is a multisystem genetic disorder that is associated with mental retardation, autism, and atypical autism. We investigated the basis for these associations by examining whether the liability to mental retardation and autism or atypical autism is related to the number and distribution of hamartomatous brain growths (cortical tubers) that characterise TS. METHODS: 18 patients consecutively referred to our clinic were assessed for the presence of autism or atypical autism, and their IQs were estimated (without awareness of brain-scan results). Brain scans were reviewed by a neuroradiologist (unaware of clinical diagnoses), and the number and location of cortical tubers was examined in relation to the liability to psychopathology. FINDINGS: Nine of the 18 patients had autism or atypical autism (two with IQ > or = 70; four with IQ 51-69, three with IQ < or = 50; eight with a history of epilepsy). The remaining patients had various other psychiatric disorders (five with IQ > or = 70; four with IQ 51-69; seven had a history of epilepsy). In the group as a whole, the number of tubers was significantly greater (p = 0.005) in patients with mental retardation (median 6 [IQR 4-9]) than in those of normal intelligence (1 [0-3]), and the degree of mental retardation was significantly correlated with the number of brain tubers (rs = 0.64; p = 0.008). Similarly, the number of tubers was significantly greater (p = 0.02) in individuals with a diagnosis of autism or atypical autism (6 [4-8]) than in those without this diagnosis (2 [1-4]). Eight of the nine patients with autism or atypical autism, but none of the non-autistic individuals, had tubers located in the temporal lobes (p = 0.0004). Otherwise, no particular distribution of cortical tubers was associated with a diagnosis of autism or atypical autism. INTERPRETATION: Our investigation provides evidence of an association between a gross, focal brain abnormality detectable on neuroimaging and autism or atypical autism. The results show the importance of scan findings in the prognosis of TS, and also suggest that temporallobe neurodevelopmental abnormalities may create a risk for autism or atypical autism.

Adolescent↗
PubMed1997

The role of duplex sonography and angiography in the investigation of carotid artery disease.

Some patients with symptomatic carotid stenoses of greater than 70 % benefit from carotid endarterectomy. This study was designed to compare the accuracy of duplex ultrasound with angiography in assessing the degree of carotid stenosis in 73 patients with symptoms of recent carotid territory ischaemia. Ultrasound was found to be most accurate in the group of patients with normal vessels or mild stenoses (0-29 %) when there was 90 % concordance between ultrasound and angiography. Ultrasound was found to be least accurate in the group of patients with severe stenoses (70-99 %) in whom it was more likely to underestimate than to overestimate the degree of stenosis. Only one patient said to have < 30 % stenosis on ultrasonography had a > 70 % stenosis on IADSA. Our results indicate that patients with normal arteries or mild disease shown by ultrasound have a very small chance of having surgically amenable lesions in the neck. Ultrasound is reliable as an exclusory screening test. However, all other stenoses should also be investigated by catheter angiography if surgery is considered. Taking angiography as the reference, only 52 % of patients with severe stenoses, which might be taken as an indication for surgery, were correctly identified on ultrasonography. Ultrasound alone is a poor technique for identifying patients for surgery and a combination of ultrasound screening with angiography for > 30 % stenoses detected by ultrasound is recommended.

Aged↗
PubMed1997

99mTechnetium HMPAO imaging in children with the Sturge-Weber syndrome: a study of nine cases with CT and MRI correlation.

Demonstration of the full extent of abnormality in patients with the Struge-Weber syndrome (SWS) is important for prognosis and in planning surgery to remove the seizure focus. We compared single-photon emission computed tomography (SPECT), MRI and CT in nine children under the age of 4 years with seizures as part of SWS, in an attempt to determine the optimal method of imaging in different clinical settings. Seven unilateral and two bilateral cases were studied by interictal 99mtechnetium hexamethylpropyleneamineoxime (HMPAO) SPECT, and contrast-enhanced CT and MRI, giving information on 11 abnormal hemispheres. All imaging modalities showed abnormalities in every child. Perfusion imaging showed focal regions of decreased uptake in 9 of 11 (82%) abnormal hemispheres and demonstrated a widespread decrease but no focal defect in 2; it also revealed crossed cerebellar diaschisis in 2 cases. CT demonstrated typical gyriform calcification in 9 of 11 (82%) affected hemispheres. Contrast-enhanced MRI showed more extensive involvement than contrast-enhanced CT in 5 of 11 (45%) cases. The area of hypoperfusion shown by SPECT was smaller than the area of contrast enhancement on MRI in 6 of 11 cases (55%), comparable in 3 (27%) and larger in 2 cases (18%). CT is sufficient to confirm the clinical diagnosis of SWS, but MRI frequently shows more extensive abnormal areas. 99mTc HMPAO imaging is a useful addition when it is important to know the full extent of the disease, for example prior to surgery. It is likely to detect areas of hypoperfusion, representing ischaemic regions, which may act as an epileptogenic focus and may not be shown by CT or MRI.

Adolescent↗
PubMed1997

Development of a quantitative competitive polymerase chain reaction for human herpesvirus 8.

A quantitative competitive polymerase chain reaction (PCR) assay for human herpesvirus 8 (HHV8) was developed. The assay uses a competitive internal control sequence which differs from the wild type sequence by the presence of an EcoRI restriction endonuclease site. The quantitative method was validated by co-amplifying known amounts of control sequence DNA and wild type DNA, and shown to accurately quantify HHV8 within the range of 10(1)-10(6) genome copies (R = 0.998). The assay was used to quantify HHV8 in sequential blood samples of a renal transplant patient diagnosed with Kaposi's sarcoma (KS). A peak viral load of 28320 genomes/ml blood was present at diagnosis of KS, which reduced to 13680 genomes after 2 days and was undetectable 4 months later. Control of HHV8 replication in this patient parallelled the cessation of immunosuppressive therapy.

Calibration↗
PubMed1997

Development of a point mutation assay for the detection of human cytomegalovirus UL97 mutations associated with ganciclovir resistance.

A point mutation assay was developed to detect the quantitative prevalence of mutations at codons 460 (M to I; M to V), 520 (H to Q), 594 (A to V) and 595 (L to F; L to S) within the UL97 gene of human cytomegalovirus which segregate with ganciclovir resistance. Synthetic mixtures of wild-type and mutant plasmids containing the UL97 gene were amplified by nested polymerase chain reaction and the 700 base pair amplicon subsequently subjected to the point mutation assay. In plasmid reconstruction experiments, there was a high correlation between experimentally derived percentage mutant with the theoretical values. The assay was then used to assess the changes in the genetic composition of the UL97 gene in three patients on prolonged ganciclovir therapy. All three patients developed genotypic resistance against ganciclovir involving mutation at codon L595S, L595F and double mutation at codons L595F and M460I. In one patient, alteration of therapy to foscarnet did not affect the composition of UL97 and virus remained genotypically resistant to ganciclovir. In contrast, in two patients whose therapy was altered to cidofovir (HPMPC), repopulation with cytomegalovirus strains carrying the wild-type (ganciclovir-sensitive) codon at positions 595 and 460 occurred. The potential use of this assay for the rapid detection of cytomegalovirus resistance in patients on long-term ganciclovir therapy is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Tuberous Sclerosis Complex: the role of neuroradiology.

Tuberous Sclerosis Complex is the second commonest phakomatosis affecting between 1 in 70,00-10,000 live births. It is a multisystem disorder but neurological disturbances are often the presenting feature and cause major morbidity/mortality. In this paper the neuroradiological and clinical features are reviewed, focusing on a rational approach to imaging children with tuberous Sclerosis Complex.

Autistic Disorder↗
PubMed1997

Angiography in non-traumatic brain haematoma. An analysis of 100 cases.

PURPOSE: The primary purpose of this project was to study the anatomical characteristics of intracerebral haematoma (ICH) in order to determine features that may negate the need for angiography in some patients. MATERIAL AND METHODS: The study was prospective and designed to investigate the underlying cause of non-traumatic ICH in 100 cases assessed by conventional angiography. Patients were excluded if there was a history of trauma or known pre-existing brain abnormality. All patients were examined with CT and angiography within 4 days of the ictus. RESULTS: Ruptured aneurysms or arteriovenous malformations (AVMs) were diagnosed on the initial angiogram in 49% of cases: 27 AVMs and 22 aneurysms. One case of superior sagittal sinus thrombosis was also detected. Vascular abnormalities were found most frequently in the under-40 age group and in cases in which subarachnoid haemorrhage, intraventricular haemorrhage or extracerebral haematoma accompanied the ICH. The temporal lobe was the most frequent anatomical location (37%). When a temporal lobe haematoma extended into the Sylvian fissure from the inferior pole of the temporal lobe or when it was associated with subarachnoid haemorrhage, structural abnormalities were found in over 90% of cases. CONCLUSIONS: There are groups of patients with ICH in whom the CT features are highly suggestive of AVM or aneurysm rupture. If the initial angiography is negative in these cases, careful follow up by repeat angiography and/or MR imaging is essential. However, potentially treatable abnormalities cannot be excluded with certainty by the distribution of the haematoma on CT alone, even if there is a history of pre-existing hypertension.

Adolescent↗
PubMed1997

Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation.

Longitudinal analysis of 162 liver transplant recipients identified 51 patients who were viremic. Virus load was determined in 47 of these patients using quantitative-competitive polymerase chain reaction. Peak virus load was significantly higher in 20 symptomatic patients than 27 asymptomatic patients (P < .0001). Elevated virus load, donor seropositivity, and total methylprednisolone dosage were risk factors for human cytomegalovirus (HCMV) disease (odds ratio [OR], 2.22/0.25 log10 increase in virus load, P = .001; OR, 4.11, P = .05; OR, 1.30/1-g increment in methylprednisolone, P = .01). Methylprednisolone and virus load were independent risk factors in a multivariate analysis (OR, 2.70/1-g increase, P = .003; OR, 1.61/0.25 log10 increase, P = .03, respectively). Virus loads of 10(4.75)-10(5.25) genomes/mL of blood were associated with an increased disease probability; the latter was shifted to lower virus loads with increasing quantities of methylprednisolone. These data illustrate the central role of virus load in HCMV pathogenesis.

Adolescent↗
PubMed1997

Cytomegalovirus (CMV) viraemia detected by polymerase chain reaction identifies a group of HIV-positive patients at high risk of CMV disease.

BACKGROUND: Cytomegalovirus (CMV) disease is a major cause of morbidity in patients with HIV infection. Despite treatment, CMV retinitis causes substantial visual loss, especially in patients with CD4 cell counts below 50 x 10(6)/l. Although routine ophthalmological screening of these patients has been recommended, no controlled trials have evaluated how frequently it should be performed. The aim of this study was to assess whether CMV polymerase chain reaction (PCR) results could direct ophthalmological screening to patients at high risk of CMV retinitis. METHODS: In a prospective study of HIV-positive patients with CD4 cell counts below 50 x 10(6)/l, CMV viraemia was detected by qualitative PCR of whole blood. Patients who were CMV PCR-viraemic were allocated to monthly virological and ophthalmological follow-up; patients who were PCR-negative received 3-monthly virological and ophthalmological follow-up. CMV viral load was determined in all CMV-positive samples using a quantitative competitive PCR. RESULTS: Nineteen out of 97 patients developed CMV disease over the first 12 months of the study. Sixteen (59%) out of 27 patients who were CMV-positive developed disease compared with three (4%) out of 70 of patients who were PCR-negative (P = 0.0001). A positive CMV PCR result was significantly associated with the development of disease (P = 0.0001), with a relative hazard of 20.15 [95% confidence interval (CI), 5.80-69.98]. Median CMV viral load was significantly higher in those individuals who went on to develop CMV disease (P = 0.02). In PCR-positive patients, each 0.25 log10 increase in viral load increased the risk of disease (relative hazard, 1.37; 95% CI, 1.15-1.63; P = 0.0004). CONCLUSIONS: CMV PCR predicts the development of CMV disease and can be used to target ophthalmological resources to those patients at highest risk of retinitis. Asymptomatic patients who are PCR-positive represent a high-risk group in whom controlled trials of pre-emptive therapy could be conducted.

AIDS-Related Opportunistic Infections↗
PubMed1997

Prospective study of human herpesvirus 6, human herpesvirus 7, and cytomegalovirus infections in human immunodeficiency virus-positive patients.

Blood samples from human immunodeficiency virus (HIV)-positive patients were monitored for cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7 by PCR. We detected CMV in 17% of the patients, HHV-6 in 6%, and HHV-7 in 3%. The viral loads of CMV were significantly higher than those of HHV-6 (P = 0.007) or HHV-7 (P = 0.01). Detection of CMV and HHV-6 was associated with low and high CD4 counts, respectively.

CD4 Lymphocyte Count↗
PubMed1997

Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction.

Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in febrile children by qualitative and quantitative polymerase chain reaction (PCR) assays. Diagnosis was based on the differential detection of viral DNA in peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile infants, but none of seven non-febrile controls, were identified with primary infections (three HHV-6, three HHV-7). These children had significantly higher viral loads in PBMC (HHV-6, median 24213 genomes/10(6) PBMC; HHV-7, median 6,040,000 genomes/10(6) PBMC) than DNA-aemic, saliva PCR positive children (HHV-6, median 1606 genomes/10(6) PBMC, p < 0.01; HHV-7, median 7089 genomes/ 10(6) PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary infections. All three children with primary HHV-7 infection had febrile convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6 and HHV-7 infections when an appropriate combination of clinical specimens is used.

DNA, Viral↗
PubMed1997

Use of polymerase chain reaction to provide prognostic information on human cytomegalovirus disease after liver transplantation.

Sixty-four consecutive liver transplant patients receiving 76 organs have been monitored for human cytomegalovirus (HCMV) in blood and urine posttransplantation using a polymerase chain reaction (PCR) assay that amplifies a 149 base pair fragment of the glycoprotein B gene. Six hundred and twenty-six blood and 310 urine samples were analysed during surveillance. Thirty-two patients had CMV infection (50%), 12 of whim progressed to HCMV disease. Detection of HCMV in either blood or urine was significantly associated with the presence or development of HCMV disease (blood, P < 0.00001; urine, P = 0.0033). All cases of HCMV disease were detected as PCR-positive in blood, although due to sampling only 50% of these patients were PCR-positive prior to disease onset. HCMV infection and disease were more likely in patients who suffered rejection (P < 0.001). In addition, the median amounts of augmented prednisolone were higher in patients with HCMV infection and disease. In all cases, augmented prednisolone preceded HCMV infection/disease. There was no statistical association between CMV infection and death. Overall, the results show that routine use of PCR for HCMV in surveillance samples of blood and urine of liver transplant recipients can provide diagnostic and prognostic information. However, its ability to provide prognostic information is directly related to the availability of appropriate surveillance samples, emphasising the importance of the routine acquisition of such samples in patient management to allow preemptive anti-HCMV therapy.

Acyclovir↗
PubMed1997

Quantity of cytomegalovirus viruria is a major risk factor for cytomegalovirus disease after renal transplantation.

Studies have shown that risk factors for human cytomegalovirus (HCMV) disease after renal transplant include primary infection (virus of donor origin infecting a non-immune individual), re-infection (virus of donor origin infecting a immune individual), and the detection of viraemia (as a marker of virus dissemination). We now report that viral load in the urine is also a significant factor in HCMV disease and is one of the main mechanisms underlying the risk associated with viraemia and donor serostatus. Longitudinal analysis of a group of 196 renal recipient identified 35 recipients who were PCR positive for HCMV in urine. Elevated viral loads were present in symptomatic patients, viraemic patients, and patients experiencing primary HCMV infection. Disease was associated with the peak quantity of virus present in the urine during the post-transplant period (P = 0.0001), with viraemia (P = 0.0003), and with transplantation of a seropositive donor (P = 0.03). Univariate logistic regression analysis showed that increases of 0.25 log10 in viral load were associated with a 179% increased risk of disease (odds ratio = 2.79; 95% C.I. 1.22-6.39; P = 0.02). This effect persisted in a multivariate logistic analysis when viraemia was incorporated (odds ratio = 2.77; 95% C.I. 1.07-7.18; P = 0.04). In contrast, the significant association between viraemia and disease observed in univariate analysis (odds ratio = 23.75; 95% C.I. 3.69-152.90; P = 0.0009) became marginally non-significant in multivariate analysis once viral load had been controlled for (odds ratio = 34.54; 95% C.I. 0.75-1599.00; P = 0.07). The computed probability of disease showed that a rapid transition occurred at viral loads between 10(5.7) and 10(6.5) genomes/ml urine in non-viraemic patients compared to viral loads between 10(5.0) and 10(5.7) genomes/ml urine in patients with concurrent viraemia. The implications of these findings for understanding HCMV pathogenesis, improving patient management, and optimising trials of antiviral treatment are discussed.

Adolescent↗
PubMed1996

Autoradiography of transferrin receptors in the human brain.

Transferrin is the major protein concerned with iron transport in the serum and may provide a route by which iron enters the brain. This study was designed to show the optimal binding conditions for in vitro transferrin receptor autoradiography and to show the regional distribution of transferrin receptors in the human brain. Optimal binding conditions were: 120 min incubation with 5.0 nM 125I-transferrin at 37 degrees C. Transferrin receptors degrade quickly even with storage at -70 degrees C, therefore binding studies should be performed within 7 days post mortem. Transferrin receptors were widely distributed in the human brain, with high density in the neocortex, moderate densities in the putamen and caudate nuclei, and very low densities in the globus pallidus and substantia nigra. Therefore transferrin receptor density shows a mismatch with the known distribution of iron in the human brain. The presence and distribution of transferrin receptors in the human brain are important because they may provide a route to deliver lipophobic substances across the blood-brain barrier by binding them to antibodies raised against transferrin receptors.

Aged↗