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Biomedical subjects

S J Price

Publications and source records attributed to S J Price.

At least 19 recordsLinked to original sources

Enhanced visualization and quantification of magnetic resonance diffusion tensor imaging using the p:q tensor decomposition.

Many scalar measures have been proposed to quantify magnetic resonance diffusion tensor imaging (MR DTI) data in the brain. However, only two parameters are commonly used in the literature: mean diffusion (D) and fractional anisotropy (FA). We introduce a visualization technique which permits the simultaneous analysis of an additional five scalar measures. This enhanced diversity is important, as it is not known a priori which of these measures best describes pathological changes for brain tissue. The proposed technique is based on a tensor transformation, which decomposes the diffusion tensor into its isotropic (p) and anisotropic (q) components. To illustrate the use of this technique, diffusion tensor imaging was performed on a healthy volunteer, a sequential study in a patient with recent stroke, a patient with hydrocephalus and a patient with an intracranial tumour. Our results demonstrate a clear distinction between different anatomical regions in the normal volunteer and the evolution of the pathology in the patients. In the normal volunteer, the brain parenchyma values for p and q fell into a narrow band with 0.976<p<1.063 x 10(-3) mm2 s(-1) and 0.15<q<1.08 x 10(-3) mm2 s(-1). The noise appeared as a compact cluster with (p,q) components (0.011, 0.141) x 10(-3) mm2 s(-1), while the cerebrospinal fluid was (3.320, 0.330) x 10(-3) mm2 s(-1). In the stroke patient, the ischaemic area demonstrated a trajectory composed of acute, sub-acute and chronic phases. The components of the lesion were (0.824, 0.420), (0.884, 0.254), (2.624, 0.325) at 37 h, 1 week and 1 month, respectively. The internal capsule of the hydrocephalus patient demonstrated a larger dispersion in the p:q plane suggesting disruption. Finally, there was clear white matter tissue destruction in the tumour patient. In summary, the p:q decomposition enhances the visualization and quantification of MR DTI data in both normal and pathological conditions.

Algorithms↗

Improved delineation of glioma margins and regions of infiltration with the use of diffusion tensor imaging: an image-guided biopsy study.

BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of treatment for malignant gliomas, is limited by our inability to accurately determine tumor margins. As a result, despite recent advances, the prognosis remains appalling. Because gliomas preferentially infiltrate along white matter tracks, methods that show white matter disruption should improve this delineation. In this study, results of histologic examination from samples obtained from image-guided brain biopsies were correlated with diffusion tensor images. METHODS: Twenty patients requiring image-guided biopsies for presumed gliomas were imaged preoperatively. Patients underwent image-guided biopsies with multiple biopsies taken along a single track that went into normal-appearing brain. Regions of interest were determined from the sites of the biopsies, and diffusion tensor imaging findings were compared with glioma histology. RESULTS: Using diffusion tissue signatures, it was possible to differentiate gross tumor (reduction of the anisotropic component, q > 12% from contralateral region), from tumor infiltration (increase in the isotropic component, p > 10% from contralateral region). This technique has a sensitivity of 98% and specificity of 81%. T2-weighted abnormalities failed to identify the margin in half of all specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor margin in gliomas. Such techniques can improve the delineation of the radiation therapy target volume for gliomas and potentially can direct local therapies for tumor infiltration.

Adolescent↗

Diffusion tensor imaging: possible implications for radiotherapy treatment planning of patients with high-grade glioma.

AIMS: Radiotherapy treatment planning for high-grade gliomas (HGG) is hampered by the inability to image peri-tumoural white-matter infiltration. Diffusion tensor imaging (DTI) is an imaging technique that seems to show white-matter abnormalities resulting from tumour infiltration that cannot be visualised by conventional computed tomography or magnetic resonance imaging (MRI). We propose a new term, the image-based high-risk volume (IHV) for such abnormalities, which are distinct from the gross-tumour volume (GTV). For IHV based on DTI, we use the term IHVDTI. This study assesses the value of DTI for the individualisation of radiotherapy treatment planning for patients with HGG. METHODS: Seven patients with biopsy-proven HGG were included in a theoretical planning exercise, comparing standard planning techniques with individualised plans based on DTI. Standard plans were generated using a 2.5 cm clinical target volume (CTV) margin added to the GTV. For DTI-based plans, the CTV was generated by adding a 1 cm margin to the IHVDTI. Estimates of normal tissue complication probability (NTCP) were calculated and used to estimate the level of dose escalation that could be achieved using the DTI-based plans. RESULTS: The use of DTI resulted in non-uniform margins being added to the GTV to encompass areas at high risk of tumour involvement, but, in six out of seven cases, the IHVDTI was encapsulated by the standard CTV margin. In all cases, DTI could be used to reduce the size of the planning-target volume (PTV) (mean 35%, range 18-46%), resulting in escalated doses (mean 67 Gy, range 64-74 Gy), with NTCP levels that matched the conventional treatment plans. CONCLUSION: DTI can be used to individualise radiotherapy target volumes, and reduction in the CTV permits modest dose escalation without an increase in NTCP. DTI may also be helpful in stratifying patients according to the degree of white-matter infiltration.

Adult↗

Detection and evaluation of intracranial aneurysms with 16-row multislice CT angiography.

AIM: The aim of this study was to assess the usefulness of 16-row multislice CT angiography (CTA) in evaluating intracranial aneurysms, by comparison with conventional digital subtraction angiography (DSA) and intraoperative findings. METHODS: A consecutive series of 57 patients, scheduled for DSA for suspected intracranial aneurysm, was prospectively recruited to have CTA. This was performed with a 16-detector row machine, detector interval 0.75 mm, 0.5 rotation/s, table speed 10mm/rotation and reconstruction interval 0.40 mm. CTA studies were independently and randomly assessed by two neuroradiologists and a vascular neurosurgeon blinded to the DSA and surgical findings. Review of CTA was performed on workstations with an interactive 3D volume-rendered algorithm. RESULTS: DSA or intraoperative findings or both confirmed 53 aneurysms in 44 patients. For both independent readers, sensitivity and specificity per aneurysm of DSA were 96.2% and 100%, respectively. Sensitivity and specificity of CTA were also 96.2% and 100%, respectively. Mean diameter of aneurysms was 6.3mm (range 1.9 to 28.1 mm, SD 5.2 mm). For aneurysms of less than 3 mm, CTA had a sensitivity of 91.7% for each reader. Although the neurosurgeon would have been happy to proceed to surgery on the basis of CTA alone in all cases, he judged that DSA might have provided helpful additional anatomical information in 5 patients. CONCLUSION: The diagnostic accuracy of 16-slice CTA is promising and appears equivalent to that of DSA for detection and evaluation of intracranial aneurysms. A strategy of using CTA as the primary imaging method, with DSA reserved for cases of uncertainty, appears to be practical and safe.

Adult↗

Characterization of an analphoid supernumerary marker chromosome derived from 15q25-->qter using high-resolution CGH and multiplex FISH analyses.

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). We report the molecular cytogenetic characterization of a new case with analphoid NMC derived from 15q25-->qter using high-resolution comparative genomic hybridization (HR-CGH) and multiplex fluorescence in situ hybridization analyses with various alpha-satellite DNA probes, all-human-centromere probe (AHC), whole chromosome painting probes, and a subtelomere probe. The propositus is a dysmorphic infant who, at age 3 months, showed accelerated growth, partial deafness, and a phenotype similar to that of the eight previously reported cases of distal 15q tetrasomy. Chromosome studies showed that he had a de novo extra SMC in 80% of cells examined. HR-CGH revealed rev ish enh(15)(q25qter). Molecular cytogenetic analysis and molecular DNA polymorphism study demonstrated that this extra SMC is an NMC containing an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q25-->qter) which originated paternally, i.e. ish der(15)(qte-->q25::q25[neocen]-->qter)(AHC-, CEP15-, WCP15+, PCP15q++). This case further elucidates the phenotype related to tetrasomy of this specific chromosome segment and represents a new report of a neocentromere on distal chromosome 15q suggesting that this region appears to be susceptible to the formation of neocentromeres.

Abnormalities, Multiple↗

Detecting glioma invasion of the corpus callosum using diffusion tensor imaging.

We present a patient with a recurrent glioblastoma and abnormalities of the corpus callosum seen on diffusion tensor MRI that were not seen on conventional imaging. These abnormalities preceded the development of the tumour. We describe the technique of diffusion tissue signatures to assess tissue infiltration by tumours compared with values from normal volunteers.

Aphasia↗

Diffusion tensor imaging of brain tumours at 3T: a potential tool for assessing white matter tract invasion?

AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)-a measure of white matter organization, was calculated for these ROI. RESULTS: The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19+/-0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3+/-0.04). CONCLUSIONS: Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas.

Adult↗

Characterization of the region containing the jcpk PKD gene on mouse Chromosome 10.

The jcpk gene on mouse Chromosome 10 causes a severe, early onset form of polycystic kidney disease (PKD) when inherited in an autosomal recessive manner. In order to positionally clone this gene, high resolution genetic and radiation hybrid maps were generated along with a detailed physical map of the approximately 500-kb region containing the jcpk gene. Additionally, sixty-nine kidney-specific ESTs were evaluated as candidates for jcpk and subsequently localized throughout the mouse genome by radiation hybrid mapping analysis. Previous studies indicating non-complementation of the jcpk mutation and 67Gso, a new PKD translocation mutant had suggested that 67Gso represents a new allele of jcpk. Fluorescence in situ hybridization (FISH) analysis using key bacterial artificial chromosome clones from the jcpk critical region, refined the 67Gso breakpoint and provided support for the allelism of jcpk and 67Gso.

Animals↗

Arachnoid cyst of the craniocervical junction: case report.

OBJECTIVE AND IMPORTANCE: An arachnoid cyst at the craniocervical junction presenting with obstructive hydrocephalus as a result of blockage of the outflow of the fourth ventricle is described. This is a very rare anatomic site, with only five other cases described in the literature. CLINICAL PRESENTATION: A 37-year-old woman presented with a 9-month history of severe neck pain, persistent vomiting, visual disturbances, and numbness of the nose, cheek, and lips. She had severe bilateral papilledema on ophthalmoscopy. Magnetic resonance imaging revealed a midline cystic lesion extending down to C2. INTERVENTION: The patient underwent posterior fossa craniectomy and excision of the arachnoid cyst. She made a full recovery and was asymptomatic at follow-up examination. CONCLUSION: The symptomatology of these rare craniocervical arachnoid cysts and their development are discussed.

Adult↗

Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation.

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. Thus, any naturally occurring genetic variants that directly affect gene expression and/or protein function would be expected to impact on progression of pathological processes involving tissue remodeling. We scanned a 2-kilobase pair promoter region and all 13 exons of the human MMP-2 gene, from a panel of 32 individuals, and we identified the position, nature, and relative allele frequencies of 15 variant loci as follows: 6 in the promoter, 1 in the 5'-untranslated region, 6 in the coding region, 1 in intronic sequence, and 1 in the 3'-untranslated region. The majority of coding region polymorphisms resulted in synonymous substitutions, whereas three promoter variants (at -1306, -790, and +220) mapped onto cis-acting elements. We functionally characterized all promoter variants by transient transfection experiments with 293, RAW264.7, and A10 cells. The common C --> T transition at -1306 (allele frequency 0.26), which disrupts an Sp1-type promoter site (CCACC box), displayed a strikingly lower promoter activity with the T allele. Electrophoretic mobility shift assays confirmed that these differences in allelic expression were attributable to abolition of Sp1 binding. These data suggest that this common functional genetic variant influences MMP-2 gene transcription in an allele-specific manner and is therefore an important candidate to test for association in a wide spectrum of pathologies for which a role for MMP-2 is implicated, including atherogenesis and tumor invasion and metastasis.

3' Untranslated Regions↗

Are goals and topics influenced by gender and modality in the initial marriage and family therapy session?

Establishment of a goal is crucial to therapy, but identification of therapeutic goals may be difficult in conjoint therapy because each participant may identify a different problem. We examined the influence of gender on ability to successfully introduce therapeutic topics in marital and family therapy by conducting two studies. The first study evaluates the ability of therapists to identify therapeutic goals that matched goals prioritized by both women and men clients on pretherapy questionnaires. The second study examines the process of initial therapy sessions to see whether gender influences a client's ability to introduce a therapeutic topic. Results suggest that therapeutic topic is influenced by the interaction of gender and treatment modality. Specifically, therapists were better able to match women's pretherapy stated goals in marital therapy than family therapy, men were more successful at introducing topics in family therapy, and women were more successful at introducing topics in marital therapy.

Adult↗

Adynamic ileus complicating lumbar laminectomy: a report of two cases.

Adynamic ileus is a well recognized complication of spinal injuries and disease. We report two cases of adynamic ileus affecting both small and large bowel following uncomplicated L4/5 laminectomy. Both patients recovered with conservative treatment, but their hospital stay was prolonged. We have found three other cases in the literature of ileus affecting only the colon following laminectomy at this same level.

Aged↗

Use of contraception in women who present for termination of pregnancy in inner London.

OBJECTIVES: To describe the contraceptive usage of women undergoing termination of pregnancy in order to identify problems with contraception, and therefore suggest ways in which contraceptive services can be improved. DESIGN: Prospective study of attenders for NHS termination of pregnancy over a three month period. SETTING: Community based assessment clinics for NHS termination of pregnancy in inner London. SUBJECTS: Two hundred and sixty-nine women asking for assessment for NHS termination of pregnancy. MAIN OUTCOME MEASURES: Source of contraception, method used around time of conception, and problems experienced. RESULTS: Respondents tell into three groups: those using contraception around the time they became pregnant; those who had ceased to use contraception; and those that had never used contraception. The method of contraception used by the majority of the first group was the condom and the main source of the method was the chemist shop. The second group had most commonly used oral contraceptives in the past and had ceased use in many cases as a result of side effects. The majority of the third group did not speak English and had limited knowledge of methods of contraception. CONCLUSIONS: High usage of chemists means women avoid service providers who could offer help and advice. Women were prepared to put themselves at risk of unwanted pregnancy rather than return for further help and the lack of knowledge about emergency birth control was of some concern. The needs of black and ethnic minority women requires detailed work to improve access and acceptability of contraceptive services.

Adolescent↗

The protein composition of gingival crevicular fluid sampled from male adolescents with no destructive periodontitis: baseline data of a longitudinal study.

Gingival crevicular fluid (GCF) is a promising source for markers of destructive periodontal diseases activity. As the initial stage of a longitudinal study into the characterization of disease markers, GCF sampled from 104 sites in 74 adolescents was examined via sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS/PAGE). In this population, which had varying degrees of gingivitis but little evidence of destructive periodontitis, there was a highly homologous GCF protein profile. The plasma components, albumin, transferrin and IgG, were major constituents of all samples. In addition, a second group of non-plasma derived proteins, with molecular weights 37 kDa, 47 kDa, 57 kDa and 59 kDa, was also commonly detected. The high frequency of occurrence of these components suggests that they may represent products of normal turnover of the periodontal tissues. Analysis of GCF sampled from patients with progressing destructive disease revealed a different SDS/PAGE profile particularly with respect to proteins of non-plasma origin. It is anticipated that the major metabolic changes which accompany the destruction of the tissues during future disease episodes in the adolescent study population will be discernible as alterations to the GCF protein profile.

Adolescent↗

The kinetics of transport of lactate and pyruvate into isolated cardiac myocytes from guinea pig. Kinetic evidence for the presence of a carrier distinct from that in erythrocytes and hepatocytes.

1. Time courses for the uptake of L-lactate, D-lactate and pyruvate into isolated cardiac ventricular myocytes from guinea pig were determined at 11 degrees C or 0 degrees C (for pyruvate) in a citrate-based buffer by using a silicone-oil-filtration technique. These conditions enabled initial rates of transport to be measured without interference from metabolism of the substrates. 2. At a concentration of 0.5 mM, transport of all these substrates was inhibited by approx. 90% by 5 mM-alpha-cyano-4-hydroxycinnamate; at 10 mM-L-lactate a considerable portion of transport could not be inhibited. 3. Initial rates of L-lactate and pyruvate uptake in the presence of 5 mM-alpha-cyano-4-hydroxycinnamate were linearly related to the concentration of the monocarboxylate and probably represented diffusion of the free acid. The inhibitor-sensitive component of uptake obeyed Michaelis-Menten kinetics, with Km values for L-lactate and pyruvate of 2.3 and 0.066 mM respectively. 4. Pyruvate and D-lactate inhibited the transport of L-lactate, with Ki values (competitive) of 0.077 and 6.6 mM respectively; the Ki for pyruvate was very similar to its Km for transport. The Ki for alpha-cyano-4-hydroxycinnamate as a non-competitive inhibitor was 0.042 mM. 5. These results indicate that L-lactate, D-lactate and pyruvate share a common carrier in guinea-pig cardiac myocytes; the low stereoselectivity for L-lactate over D-lactate and the high affinity for pyruvate distinguish it from the carrier in erythrocytes and hepatocytes. The metabolic roles for this novel carrier in heart are discussed.

Animals↗