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Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

At least 37 records · Page 2Linked to original sources
PubMed2004

Clinical features, aetiology and outcome of empyema in children in the north east of England.

BACKGROUND: The incidence of empyema in children in the UK is increasing. The reason for this is unclear. A prospective study was undertaken to investigate the clinical features, aetiology, and outcome of cases of empyema and parapneumonic effusion presenting to a tertiary paediatric respiratory centre between February 1997 and August 2001. METHOD: Routine bacterial culture of blood and pleural fluid was performed for 47 cases. Forty three pleural fluid specimens, culture negative for pneumococcus, were analysed for pneumococccal DNA by real time polymerase chain reaction (PCR). Penicillin susceptibility was determined for DNA positive specimens using complementary PCR assay. Capsular serotype specific antigen detection was by enzyme immunoassay (EIA) using monoclonal antibodies to serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Clinical data were obtained from patient notes, supplemented by a postal questionnaire. RESULTS: The median (range) age of the patients was 5.6 (0.6-16.9) years and 70% were male. The median (range) duration of illness before referral to hospital was 5 (0-25) days. Forty five (96%) had received antibiotics before referral; 32 (68%) required decortication and eight (21%) thoracocentesis. Median postoperative stay was 4 days (2-8). Thirty two (75%) pneumococcal culture negative specimens were pneumococcal DNA positive; 17 (53%) of these were serotype 1. All were penicillin sensitive. CONCLUSIONS: Pneumococcus is the major pathogen in childhood empyema and serotype 1 is the prevalent serotype. This has implications for vaccine development and immunisation strategy as the current 7-valent pneumococcal conjugate vaccine does not protect against serotype 1.

Adolescent↗
PubMed2003

MRI findings in Susac's syndrome.

BACKGROUND: Susac syndrome (SS) is a self-limited syndrome, presumably autoimmune, consisting of a clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. All three elements of the triad may not be present or recognized, and MR imaging is often necessary to establish the diagnosis. OBJECTIVE: To determine the spectrum of abnormalities on MRI in SS. METHODS: The authors reviewed the MR images of 27 previously unreported patients with the clinical SS triad, and 51 patients from published articles in which the MR images were depicted or reported. RESULTS: All 27 patients had multifocal supratentorial white matter lesions including the corpus callosum. The deep gray nuclei (basal ganglia and thalamus) were involved in 19 (70%). Nineteen (70%) also had parenchymal enhancement and 9 (33%) had leptomeningeal enhancement. Of the 51 cases from the literature, at least 32 had callosal lesions. The authors could not determine the presence of callosal lesions in 18 of these patients, and only one was reported to have a normal MRI at the onset of encephalopathy. CONCLUSIONS: The MR scans in SS show a rather distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum. There is often deep gray matter, posterior fossa involvement, and frequent parenchymal with occasional leptomeningeal enhancement. The central callosal lesions differ from those in demyelinating disease, and should support the diagnosis of SS in patients with at least two of the three features of the clinical triad.

Adult↗
PubMed2003

Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1.

Gain of 12p material is invariably associated with testicular germ cell tumors (TGCTs) of adolescents and adults, most usually as an isochromosome 12p. We analyzed TGCTs with i(12p) using a global approach to expression profiling targeting chromosomes (comparative expressed sequence hybridization, CESH). This indicated overexpression of genes from 12p11.2-p12.1 relative to testis tissue and fibroblasts. The nonseminoma subtype showed higher levels of expression than seminomas. Notably, 12p11.2-p12.1 is amplified in about 10% of TGCTs and CESH analysis of such amplicon cases showed high levels of overexpression from this region. Microarray analysis, including cDNA clones representing most UniGene clusters from 12p11.2-p12.1, was applied to DNA and RNA from 5 TGCTs with amplification of 12p11.2-p12.1 and seven TGCTs with gain of the entire short arm of chromosome 12. Expression profiles were consistent with the CESH data and overexpression of EST595078, MRPS35 and LDHB at 12p11.2-p12.1 was detected in most TGCTs. High-level overexpression of BCAT1 was specific to nonseminomas and overexpression of genes such as CMAS, EKI1, KRAS2, SURB7 and various ESTs correlated with their amplification. Genes such as CCND2, GLU3, LRP6 and HPH1 at 12p13 were also overexpressed. The overexpressed sequences identified, particularly those in the region amplified, represent candidate genes for involvement in TGCT development.

Adolescent↗
PubMed2003

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling.

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Cluster Analysis↗
PubMed2003

Implicit memory formation in sedated ICU patients after cardiac surgery.

BACKGROUND: Recent research into memory formation under sedation has generated conflicting results. We investigated explicit and implicit memory in ICU patients during moderate to deep propofol sedation following cardiac surgery. METHODS: Two different methods of memory testing were used; (1). free-association (F-A) word-pair testing (n=33) to test conceptual implicit memory and (2). process dissociation procedure (PDP) (n=26) to detect perceptual implicit and explicit memory. One hour after surgery, whilst sedated, the F-A group received one of two lists of 10 category-exemplar word-pairs through headphones, while the PDP group was presented with one of two lists of 16 five-letter words. When awake and co-operative, the F-A group was tested using F-A testing, and the PDP group was tested using the PDP. RESULTS: The F-A group had a mean (SD) correct response rate of 7 (9)% for the target list, and 9 (8)% for the distractor list. The PDP group had a mean (SD) correct response rate of 11 (14) and 10 (13)% for the inclusion and exclusion lists, respectively, with mean correct response rates of 13 (14)% for both the corresponding distractor lists. Neither group showed any significant differences between their responses and a list of distractor words (Wilcoxon tests). CONCLUSION: We found no evidence for memory formation in post-cardiac surgery patients under moderate to deep propofol sedation.

Adult↗
PubMed2003

Developing clinically relevant and reproducible symptom-defined populations for cancer diagnostic research in general practice using a community survey.

BACKGROUND: In developing cancer diagnostic studies, there is a particular need for the population of patients with symptoms of possible oncological significance who consult the GP in 'real life' to be comparable with the group of individuals with symptoms constructed as part of a research project. OBJECTIVES: The objective of this study was to seek to assess whether a community-based symptom survey can be harnessed in order to produce clinically relevant and reproducible populations within which studies of more detailed indicants could be undertaken. METHOD: A total of 3629 patients registered with a general practice at Winterton, UK, were sent a questionnaire enquiring about 10 symptoms of possible oncological significance together with their consultation intention in relation to these symptoms. Up to 1 month later, an identical questionnaire was applied to all patients reporting at least one symptom, and more detailed information was obtained by research nurses on each symptom. RESULTS: The overall response rate was 64.4%, and 850 patients reported one or more symptoms. For the majority of symptom reports, there was moderate to substantial agreement between the two applications of the questionnaire. The question on blood in the motions/toilet pan or on the toilet paper demonstrated almost perfect agreement. Slight agreement was found for abdominal pain for longer than 4 weeks and for black/tarry motions. In relation to the reliability of the patient consultation intention, there was substantial/moderate agreement for actions related to the majority of symptoms. For all symptoms, there was also a greater level of agreement for past activity than future intent. CONCLUSION: The results of the study provide some support for a community survey as a mechanism to develop 'clinically relevant' populations for the iatrotropic symptoms rectal bleeding or indigestion/heartburn within which studies of more detailed indicants could be undertaken. There is also consistency with the work of others in relation to the numbers and characteristics of patients within the 'clinically relevant' population.

Aged↗
PubMed2002

Octopamine modulates spermathecal muscle contractions in Locusta migratoria.

Octopamine was identified in the spermathecal tissue of Locusta migratoria using HPLC and immunohistochemical techniques. Octopamine-like immunoreactive unpaired median neurons were identified in the VIIth and VIIIth (terminal) abdominal ganglia and octopamine-like immunoreactive axons were present in the ventral ovipositor nerve (branches from this nerve innervate the spermatheca). Stimulatory actions of octopamine on myogenic and neurogenic contractions were observed. Dose-dependent increases in the frequency of myogenic contractions and the amplitude of neurogenic contractions were elicited by the application of octopamine to the spermathecal muscle. Non-sustained basal tension increases were noted in some preparations, although these were not found to be dose-dependent. SchistoFLRFamide (PDVDHVFLRFamide) inhibited octopamine-induced contractions by a maximum of about 30%. In the presence of 3-isobutyl-1 -methylxanthine, octopamine increased cAMP levels in all regions of the spermathecal. The largest increase in cAMP content was found in the spermathecal sac, followed by the straight duct and coil duct. Phentolamine blocked octopamine-induced increases in cAMP levels and abolished the actions of octopamine on myogenic contractions.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Indirect effects of heavy metals on parasites may cause shifts in snail species compositions.

We studied the direct and indirect effects of pollution on the distributions and abundances of two closely related species of pulmonate freshwater snails. Physella columbiana is more numerous at heavy metal-polluted lakes, and Lymnaea palustris is more numerous at reference lakes. Both species are present at all sites, as are predatory bluegill sunfish (Lepomis macrochirus). The direct effects examined included the snails' growth and reproduction in both the presence and absence of heavy metals and their short-term survival when exposed to large concentrations of heavy metals. The indirect effects were the species' ability to elude capture by sunfish and the diversity and abundance of parasites within the snails. We found that heavy metals had little direct effect on growth and reproduction and that both species acquired similar levels of metals in their tissues. Interestingly, P. columbiana (the more abundant species in polluted lakes) actually exhibited higher recruitment in the absence of metals than did L. palustris (reference lakes). L. palustris has life history characteristics that favor increased growth and reduced reproduction. These characteristics resulted in decreased predation of adults by gape-limited predators and a greater ability to cope with heavy parasite burdens. P. columbiana exhibited slower growth, which resulted in increased predation although higher reproduction rates may compensate.The major effect of heavy metals on species distributions was indirect on the snails' parasites. Parasites appeared to be very susceptible to metals, and this resulted in lower parasite diversity and intensities at polluted sites for both species of snails. P. columbiana may only be able to outcompete L. palustris at polluted sites due to the indirect effects of heavy metals; the negative effect of heavy metals on parasites, and a proposed negative effect of metals on the foraging ability of sunfish that favors the faster-reproducing P. columbiana.

Animals↗
PubMed2002

Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland.

The prion protein (PrP) genotypes of all cull sheep originating from four scrapie-affected farms in Shetland in 1998-1999 were determined and a representative sample of the different genotypes was selected for necropsy. Samples of brain and selected viscera were removed from 159 such sheep aged 2-11 years. These samples were examined immunohistochemically and by Western blotting for infection-specific forms of PrP. None of the sheep bearing the following genotypes showed any evidence of PrP accumulation in brain, intestine, selected lymph nodes or the cranial mesenteric ganglia: ARQ/ARQ (n = 41), ARQ/ARH (n = 12), ARH/ARH (n = 2), ARQ/ARR (n = 24), ARR/ARR (n= 2). In five of 71 sheep bearing a single VRQ allele, PrP accumulation was detected immunohistochemically in viscera or brain, or both. These results suggested that only a small proportion of susceptible sheep showed evidence of infection (accumulation of PrP) on the farms studied, and that even sheep of the most susceptible genotype (VRQ/VRQ) did not invariably develop disease in an infected environment. Furthermore, there was no evidence that, in sheep of semi-resistant or fully resistant genotypes, infection could be sequestered within the lymphoreticular system or peripheral nervous system and thereby provide a possible "carrier" source of infection. Rather, the data suggested that some sheep, possibly because they had been exposed to a relatively low infective dose, became infected and accumulated the infective agent over a protracted pre-clinical phase of the disease. Such sheep might be potentially infective for many years. In two VRQ/ARR genotype sheep, PrP was confined to the brain. Infection-specific PrP was also confined to the brain in two of 24 clinical cases of VRQ/ARQ scrapie. Thus, direct neuroinvasion, apparently without a prior phase of replication in the lymphoreticular system, occurred in a proportion of VRQ/ARQ sheep. Possibly it may occur in all sheep of the VRQ/ARR genotype. The factors responsible for direct neuroinvasion are not understood. However, it cannot be attributed to genotype alone.

Animals↗
PubMed2002

A covalently stabilised glucose responsive gel formulation with a Carbopol carrier.

A novel glucose-responsive gel formulation was stabilised via covalent coupling to a carbomer resin. The gel formed between the plant lectin, concanavalin A and specific polysaccharides was stabilised to minimise leaching of gel components into the surroundings. This was required to prevent toxicity and to preserve the working mechanism of the formulation. Increased gel stability was introduced by covalently bonding amine groups present on the lysine residues of concanavalin A to carboxylic moieties on Carbopol 974P NF using carbodiimide chemistry. The introduction of dextran then produced a glucose-responsive formulation that transformed from gel to sol in the presence of free glucose. The rheological properties and in vitro component and insulin release of the carbomer-stabilised gel were evaluated. A decrease in viscosity over a chosen glucose concentration range was exhibited by the carbomer-based gel. The testing of such a formulation in in vitro diffusion experiments revealed that the leaching of concanavalin A from the covalently coupled gels was restricted significantly with respect to a non-coupled gel. Insulin delivery in response to glucose in the physiologically relevant glucose concentration range was demonstrated using the carbomer-stabilised gel at 37 degrees C. The performance of this novel self-regulating drug delivery system has been improved in terms of increased gel stability with reduced component leaching.

Acrylic Resins↗
PubMed2002

Assessment of G-CSF stimulated BM hematopoietic stem cells in normal donors.

BACKGROUND: The clinical use of G-CSF has recently been expanded to include mobilization of stem cells for both autologous and allogeneic transplantation. Most of the published studies have focused on stem cells released into the peripheral blood (PB) after G-CSF treatment. However, little is known about the effects of G-CSF on BM. This study evaluated the concurrent effects of short-term G-CSF on both BM and PB stem and progenitor cells in normal individuals. METHODS: Volunteers received 5 or 10 microg/kg of G-CSF for 5 consecutive days (Days 1-5). On Days 0, 3, 6, 9 and 15, BM and PB samples were obtained. Flow cytometry and functional assay were performed to analyze stem cells, subpopulations, adhesion molecules, colony-forming units and LTCIC. RESULTS: The total nucleated cells and absolute numbers of CD34(+)/mL showed a similar response pattern in both BM and PB, with a peak around Day 6 that returned to baseline levels by Day 15. However, there was a reciprocal change in the percentage of CD34(+) cells between BM and PB compartments. The expressions of adhesion molecule showed an up- and down-regulation of alpha4 and alpha5 integrin subunits, respectively, also correlated with the CD34(+) mobilization patterns. DISCUSSIONS: The functional characterization of integrins, and further clinical examination of G-CSF-stimulated BM is warranted. G-CSF-stimulated BM maybe considered as an alternative source of stem cells in transplantation.

Adult↗
PubMed2002

Covalent coupling of concanavalin A to a Carbopol 934P and 941P carrier in glucose-sensitive gels for delivery of insulin.

A novel glucose-sensitive gel formulation, containing concanavalin A and specific polysaccharides, was stabilised via covalent coupling to two structurally different carbomers. The bonding was done to minimise leaching of gel components thereby preventing toxicity and preserving the working mechanism of the gel. Increased gel stability was introduced by covalently bonding amine groups present on the lysine residues of concanavalin A to carboxylic moieties on Carbopol 934P NF and 941P NF using carbodiimide chemistry. The introduction of dextran then produced a glucose-sensitive formulation that transformed from gel to sol in the presence of free glucose. Rheological examination of glucose-sensitive gels stabilised in this way and containing varying concentrations of glucose was conducted with a cone and plate viscometer used in continual rotation mode. A decrease in viscosity over the chosen glucose concentration range was exhibited by both carbomer-stabilised formulations. The subsequent testing of such formulations in in-vitro diffusion experiments revealed that the leaching of concanavalin A from the covalently coupled gels is restricted significantly with respect to non-coupled formulations. In addition, insulin delivery in response to glucose in the physiologically relevant glucose concentration range has been demonstrated using the carbomer-stabilised gels at 37 degrees C. The performance of this self-regulating drug delivery system has been improved in terms of increased gel stability with reduced component leaching.

Acrylates↗
PubMed2002

Randomized comparison of the quality of realtime fetal ultrasound images transmitted by ISDN and by IP videoconferencing.

We compared the quality of realtime fetal ultrasound images transmitted using ISDN and IP networks. Four experienced obstetric ultrasound specialists viewed standard recordings in a randomized trial and rated the appearance of 30 fetal anatomical landmarks, each on a seven-point scale. A total of 12 evaluations were performed for various combinations of bandwidths (128, 384 or 768 kbit/s) and networks (ISDN or IP). The intraobserver coefficient of variation was 2.9%, 5.0%, 12.7% and 14.7% for the four observers. The mean overall ratings by each of the four observers were 4.6, 4.8, 5.0 and 5.3, respectively (a rating of 4 indicated satisfactory visualization and 7 indicated as good as the original recording). Analysis of variance showed that there were no significant interobserver variations nor significant differences in the mean scores for the different types of videoconferencing machines used. The most significant variable affecting the mean score was the bandwidth used. For ISDN, the mean score was 3.7 at 128 kbit/s, which was significantly worse than the mean score of 4.9 at 384 kbit/s, which was in turn significantly worse than the mean score of 5.9 at 768 kbit/s. The mean score for transmission using IP was about 0.5 points lower than that using ISDN across all the different bandwidths, but the differences were not significant. It appears that IP transmission in a private (non-shared) network is an acceptable alternative to ISDN for fetal tele-ultrasound and one deserving further study.

Computer Communication Networks↗
PubMed2001

Interactive memory systems in the human brain.

Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates. A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies and neuroimaging, activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning.

Adult↗