Search PubMed⌕ Search

Biomedical subjects

Paul D Griffiths

Publications and source records attributed to Paul D Griffiths.

At least 37 records · Page 2Linked to original sources
PubMed2005

Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy?

Fetal and perinatal autopsy provides essential diagnostic information not only for parents but also for medical audit and clinical trials. The autopsy rate is decreasing throughout the world for numerous reasons. Medical imaging has always been part of the autopsy process, but in the last decade there has been increased interest in imaging as additional to or a replacement for autopsy. This is especially so with the wider availability of magnetic resonance (MR) scanners that are able to provide detailed anatomy of all body structures as well as having the potential to provide information about histopathological patterns of injury. Postmortem MR imaging (MRI) provides similar information to autopsy for gross pathology of most organ systems. It often provides more information in cases of central nervous system abnormalities, but is less accurate for cardiac abnormalities. Targeted, image-guided biopsy may allow histological diagnosis following postmortem MRI.

Autopsy↗
PubMed2005

Cytomegalovirus.

PURPOSE OF REVIEW: To identify recent developments in the management of congenital cytomegalovirus infection which continues to exact a heavy toll on the developing central nervous system. RECENT FINDINGS: A major advance is the publication of a randomized controlled trial showing that hearing loss is significantly decreased by ganciclovir. This treatment should now be offered to all neonates who would have met the eligibility criteria of the trial, that is proven congenital infection with central nervous system involvement when treatment is begun within 1 month of birth. A second major advance is the use of stored dried blood spots to detect cytomegalovirus DNA and so differentiate congenital infection from perinatal infection. This approach has the potential to diagnose a proportion of cases of hearing loss and mental retardation which are currently labelled idiopathic. A third major advance is the clinical evaluation of vaccines against cytomegalovirus. Experiments with guinea pig cytomegalovirus show reduced fetal mortality and congenital infection among dams given vaccines containing the glycoprotein B of the virus. A different vaccine glycoprotein B construct has been shown to be immunogenic and well tolerated in healthy adult and paediatric humans. Recent reviews from the Institute of Medicine and the National Vaccine Advisory Committee emphasize the financial and humanitarian justifications for developing cytomegalovirus vaccines as a high priority. SUMMARY: Substantial progress has recently been made in diagnosis and treatment. If additional financial support were to be made available to evaluate existing vaccine candidates in controlled clinical trials, congenital cytomegalovirus could potentially become a vaccine-preventable disease.

Animals↗
PubMed2004

Spurious leptomeningeal enhancement on immediate post-operative MRI for paediatric brain tumours.

Immediate post-operative MRI has been recommended as an accurate and robust method to assess residual brain tumour. Early enhancement at the resection margin and in the dura is well recognized, but we describe two cases of enhancement in the basal cisterns on immediate post-operative MRI that resolved on follow-up. The underlying cause of the enhancement remains to be elucidated, but it should be recognized that leptomeningeal enhancement may occur after surgery and that this does not necessarily imply tumour spread.

Biopsy↗
PubMed2004

Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Before highly active antiretroviral therapy (HAART) became available, cytomegalovirus was a major cause of opportunistic infection in HIV-infected patients and was associated with accelerated progression to AIDS and death. We have investigated whether cytomegalovirus viraemia remains a significant risk factor for progression of HIV disease and death in the era of HAART. METHODS: 374 patients whose CD4-cell count had ever been below 100 per microL were enrolled in a prospective study. Serial blood samples were tested for cytomegalovirus by PCR. Rates of new cytomegalovirus disease, new AIDS-defining disorders, and death were calculated over a median follow-up of 37 months after stratification according to baseline and most recent cytomegalovirus PCR status at any point during follow-up. FINDINGS: Of 2969 PCR assays, 375 (12.6%) were positive for cytomegalovirus DNA. 259 (69.3%) patients were persistently negative for cytomegalovirus by PCR; 15 were persistently positive; and 100 were intermittently positive and negative. In multivariate models, cytomegalovirus PCR-positive status as a time-updated covariate was significantly associated with increased relative rates of progression to a new AIDS-defining disorder (2.22 [95% CI 1.27-3.88] p=0.005) and death (4.14 [1.97-8.70] p=0.0002). INTERPRETATION: Detection of cytomegalovirus in blood by PCR continues to identify patients with a poor prognosis, even in the era of HAART. Randomised controlled clinical trials of drugs active against cytomegalovirus are needed to investigate whether this virus is a marker or a determinant of HIV disease progression.

AIDS-Related Opportunistic Infections↗
PubMed2004

Mutations in microcephalin cause aberrant regulation of chromosome condensation.

Microcephalin (MCPH1) is a gene mutated in primary microcephaly, an autosomal recessive neurodevelopmental disorder in which there is a marked reduction in brain size. PCC syndrome is a recently described disorder of microcephaly, short stature, and misregulated chromosome condensation. Here, we report the finding that MCPH1 primary microcephaly and PCC syndrome are allelic disorders, both having mutations in the MCPH1 gene. The two conditions share a common cellular phenotype of premature chromosome condensation in the early G2 phase of the cell cycle, which, therefore, appears to be a useful diagnostic marker for individuals with MCPH1 gene mutations. We demonstrate that an siRNA-mediated depletion of MCPH1 is sufficient to reproduce this phenotype and also show that MCPH1-deficient cells exhibit delayed decondensation postmitosis. These findings implicate microcephalin as a novel regulator of chromosome condensation and link the apparently disparate fields of neurogenesis and chromosome biology. Further characterization of MCPH1 is thus likely to lead to fundamental insights into both the regulation of chromosome condensation and neurodevelopment.

Animals↗
PubMed2004

Susceptibility of porcine cytomegalovirus to antiviral drugs.

OBJECTIVES: Re-activation of porcine cytomegalovirus (PCMV) in the xenograft has been reported in pig-to-baboon models of xenotransplantation and is associated with invasive disease and consumptive coagulopathy. If xenotransplantation of porcine organs into human recipients is to proceed, donor organs will have to be free from a wide range of infectious agents including PCMV. However, it is prudent to characterize the antiviral susceptibility of this virus. We therefore investigated the effect of selected antiviral agents, currently licensed for the treatment of human herpesvirus infections, on PCMV replication. METHODS: Antiviral susceptibility was determined using real-time PCR and indirect immunofluorescence measurements in a porcine fallopian tube cell line infected with PCMV. RESULTS: PCMV replication was significantly inhibited by ganciclovir and cidofovir (both EC(50) < 1 mg/L) and to a lesser extent by foscarnet (EC(50) within range 25-50 mg/L) and aciclovir (EC(50) > 25 mg/L). CONCLUSIONS: These results show that, if it proves necessary, ganciclovir and cidofovir should be considered as first-line drugs to treat PCMV infections in xenograft recipients.

Animals↗
PubMed2004

A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients.

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir (5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log10 higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo.

Adolescent↗
PubMed2004

Sequence variability of the alpha-chemokine UL146 from clinical strains of human cytomegalovirus.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects a variety of cell types in vivo. A region (referred to as UL/b') present in the Toledo strain of HCMV and low passage clinical isolates contains 22 additional genes, which are absent in the highly passaged laboratory strain AD169. One of these genes, UL146, encodes an alpha-chemokine. PCR amplification and sequencing of this gene from serial samples obtained from transplant recipients and samples from infants with suspected congenital HCMV infection, revealed that UL146 is a hypervariable gene in vivo. However, genetic changes were highly conserved in individuals and in renal transplant recipients multiple genotypes of UL146 were present. The majority of strains characterized maintained the conserved ELRCXC motif present in the Toledo strain of HCMV. These results provide further evidence that AD169 does not represent the authentic virus in vivo and although Towne and Toledo are more representative, major genetic differences still exist. Mixed populations of HCMV strains occur in vivo so cloning of these strains is essential if an authentic genotype is to be defined.

Chemokines, CXC↗
PubMed2004

Finite-difference simulations of 3He diffusion in 3D alveolar ducts: comparison with the "cylinder model".

Time-dependent measurements of 3He diffusion in the lung could provide an accurate method to quantify alveolar length scales and the progression of diseases such as emphysema. However, the apparent diffusion coefficient (ADC) presents a complex problem to model and solve analytically. Here, finite-difference methods were used to simulate diffusion in 3D alveolar ducts. The results were compared to the only available analytical model--the "cylinder model"--from which it is possible to estimate the average radii of the alveolar ducts from in vivo data. The trend in data observed from simulations was found to agree well with the cylinder model. However, the cylinder model always overestimated the average radii of the simulated alveolar ducts. The simulations also demonstrated that the measurement of the longitudinal ADC (along the alveolar ducts) should be sensitive to early emphysematous changes, whereas the measured radii should be far less sensitive.

Computer Simulation↗
PubMed2004

Investigating 3He diffusion NMR in the lungs using finite difference simulations and in vivo PGSE experiments.

Finite difference simulations have been used to model (3)He gas diffusion in simulated lung tissue. The technique has the advantage that a wide range of structural models and diffusion-sensitizing gradient waveforms can be investigated, for which analytical methods would otherwise be virtually impossible. Results from simulations and in vivo pulsed-gradient-spin-echo (PGSE) experiments show that the apparent diffusion coefficient (ADC) is a function of diffusion time and gradient strength, and suggests diffusion is locally anisotropic. The simulations have been compared to recent work on an analytical model that characterizes lung tissue as a series of independent cylinders. The results presented may have clinical implications for (3)He ADC measurements in assessing lung diseases such as chronic-obstructive-pulmonary-disease.

Adult↗
PubMed2004

Genetic content of wild-type human cytomegalovirus.

The genetic content of wild-type human cytomegalovirus was investigated by sequencing the 235 645 bp genome of a low passage strain (Merlin). Substantial regions of the genome (genes RL1-UL11, UL105-UL112 and UL120-UL150) were also sequenced in several other strains, including two that had not been passaged in cell culture. Comparative analyses, which employed the published genome sequence of a high passage strain (AD169), indicated that Merlin accurately reflects the wild-type complement of 165 genes, containing no obvious mutations other than a single nucleotide substitution that truncates gene UL128. A sizeable subset of genes exhibits unusually high variation between strains, and comprises many, but not all, of those that encode proteins known or predicted to be secreted or membrane-associated. In contrast to unpassaged strains, all of the passaged strains analysed have visibly disabling mutations in one or both of two groups of genes that may influence cell tropism. One comprises UL128, UL130 and UL131A, which putatively encode secreted proteins, and the other contains RL5A, RL13 and UL9, which are members of the RL11 glycoprotein gene family. The case in support of a lack of protein-coding potential in the region between UL105 and UL111A was also strengthened.

Amino Acid Sequence↗
PubMed2004

Ultrafast magnetic resonance imaging of the neonate in a magnetic resonance-compatible incubator with a built-in coil.

BACKGROUND: Magnetic resonance (MR) imaging of the neonate is important clinically, because this group of patients often has complex and multiple problems due to prematurity and developmental abnormalities. MR imaging usually involves moving neonates away from their controlled environment to the scanner. OBJECTIVE: In this study we present the results of our initial experience with an MR-compatible incubator used on a 1.5-T system. METHODS: Seven neonates were imaged at 1.5 T without sedation or anesthesia. Images were obtained by using single-shot fast spin echo, 3-dimensional Fourier transfer gradient echo, and diffusion-weighted sequences. In 4 cases, time-of-flight angiography was performed. RESULTS: All 7 neonates were stable throughout the scan time (10-21 minutes). Experienced observers graded the images for quality, and all were graded excellent or good. In no case was the image quality poor. CONCLUSION: Neonates can be imaged safely by using an MR-compatible incubator and fast image sequences. This method should allow neonates to be imaged by MR in sites at which a dedicated neonatal MR scanner is not available.

Brain↗
PubMed2004

Pediatric head and neck lesions: assessment of vascularity by MR digital subtraction angiography.

BACKGROUND AND PURPOSE: Pediatric head and neck lesions can be difficult to characterize on clinical grounds alone. We investigated the use of dynamic MR digital subtraction angiography as a noninvasive adjunct for the assessment of the vascularity of these abnormalities. METHODS: Twelve patients (age range, 2 days to 16 years) with known or suspected vascular abnormalities were studied. Routine MR imaging, time-of-flight MR angiography, and MR digital subtraction angiography were performed in all patients. The dynamic sequence was acquired in two planes at one frame per second by using a thick section (6-10 cm) selective radio-frequency spoiled fast gradient-echo sequence and an IV administered bolus of contrast material. The images were subtracted from a preliminary mask sequence and viewed as a video-inverted cine loop. RESULTS: In all cases, MR digital subtraction angiography was successfully performed. The technique showed the following: 1) slow flow lesions (two choroidal angiomas, eyelid hemangioma, and scalp venous malformation); 2) high flow lesions that were not always suspected by clinical examination alone (parotid hemangioma, scalp, occipital, and eyelid arteriovenous malformations plus a palatal teratoma); 3) a hypovascular tumor for which a biopsy could be safely performed (Burkitt lymphoma); and 4) a hypervascular tumor of the palate (cystic teratoma). CONCLUSION: Our early experience suggests that MR digital subtraction angiography can be reliably performed in children of all ages without complication. The technique provided a noninvasive assessment of the vascularity of each lesion that could not always have been predicted on the basis of clinical examination or routine MR imaging alone.

Adolescent↗
PubMed2003

Enhancement of humoral immune responses to a human cytomegalovirus DNA vaccine: adjuvant effects of aluminum phosphate and CpG oligodeoxynucleotides.

A human cytomegalovirus (HCMV) glycoprotein B (gpUL55) DNA vaccine has been evaluated in BALB/c mice. Intramuscular immunization of these mice with pRc/CMV2-gB resulted in the generation of high levels of gpUL55-specific antibody (geometric mean titer [GMT] 1:8900) and neutralizing antibody (GMT 1:74) after 2 booster doses given 5 and 10 weeks after primary inoculation. Emulsifying the construct with the aluminum phosphate gel adjuvant Adju-Phos before immunization enhanced gpUL55-specific antibody responses (GMT 1:17800, P = 0.04). Co-immunization with CpG oligodeoxynucleotides was shown to enhance levels of neutralizing antibodies generated by immunization of mice with a pRc/CMV2-gB/Adju-Phos emulsion (P = 0.04). The results provide a rationale for evaluating combinations of other HCMV proteins for incorporation into a multi-target DNA vaccine, and for the optimization of adjuvant usage, to elicit enhanced levels of neutralizing antibodies. 2003.

Adjuvants, Immunologic↗
PubMed2003

B1AC-MAMBA: B1 array combined with multiple-acquisition micro B0 array parallel magnetic resonance imaging.

The combination of an in-plane B(1) sensitivity encoding (SENSE) technique with a simultaneous multiple-slice B(0) field step technique (multiple-acquisition micro B(0) array (MAMBA)) has produced high scan time reduction factors (R < or = 8). In this study, two slices were acquired simultaneously in combination with x2 and x4 SENSE in-plane encoding using a MAMBA stepped B(0) field coil inside a four-channel phased-array coil system. Experiments were performed on a 1.5 T Infinion system (Philips Medical Systems, Cleveland, OH). The signal-to-noise ratio (SNR) was reduced with higher R factors, as was expected from the reduced number of acquisitions used to create the unaliased images. The combination of SENSE and MAMBA offers great promise for reducing scan times through parallel acquisition while at the same time reducing the number of RF channels required by a factor equal to the number of field steps employed. The B(1) array combined with MAMBA (B(1)AC-MAMBA) technique is applicable when the length of an object is much greater than its diameter, as in scanning limbs or in whole-body screening for disease.

Artifacts↗
PubMed2003

Dynamic radial projection MRI of inhaled hyperpolarized 3He gas.

A radial projection sliding-window sequence has been developed for imaging the rapid flow of (3)He gas in human lungs. The short echo time (TE) of the radial sequence lends itself to fast repetition times, and thus allows a rapid update in the image when it is reconstructed with a sliding window. Oversampling in the radial direction combined with angular undersampling can further reduce the time needed to acquire a complete image data set, without significantly compromising spatial resolution. Controlled flow phantom experiments using hyperpolarized (3)He gas exemplify the temporal resolution of the method. In vivo studies on three healthy volunteers, one patient with chronic obstructive pulmonary disease (COPD), and one patient with hemiparalysis of the right diaphragm demonstrate that it is possible to accurately resolve the passage of gas down the trachea and bronchi and into the peripheral lung.

Fourier Analysis↗