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Biomedical subjects

J Cooke

Publications and source records attributed to J Cooke.

At least 19 recordsLinked to original sources
PubMed2001

What role do nurses play in Type 2 diabetes care in the community: a Delphi study.

OBJECTIVES: To identify the views of nurses on their current and future roles in care in the community for people with Type 2 diabetes. METHOD: A two-round Delphi study was used to elicit, and assess consensus on opinions from random samples of practice nurses, with a substantial role in the management of diabetes patients and diabetes specialist nurses. Both groups had defined levels of expertise in diabetes care and worked in Great Britain. The study instrument in round one comprised a questionnaire with 10 statement headings inviting opinions on the nursing role in the management and care of people with Type 2 diabetes. In the second round levels of agreement were elicited from responders on collated opinions from round one. The initial questionnaire also included closed questions to obtain a profile of current care delivered. RESULTS: Responders were 97 practice nurses and 69 diabetes specialist nurses with second round response rates of 93% and 86%, respectively. The 47 themes raised could be grouped under headings of clinical practice, responsibility, communication, knowledge, education/experience, rewards, and patients' roles. Many were common to several statements and both nurse groups. The level of agreement on the themes fed back was high, 85% of the 165 items achieved greater than 80% agreement. Agreement occurred for factors relating to clinical effectiveness, audit, knowledge, education and experience. Dissent occurred both within and between individual nurse groups on issues of responsibility, prescribing, service delivery, resources, and patient factors. CONCLUSIONS: This Delphi study has identified key areas of consensus on the management of care for people with Type 2 diabetes in the community but also areas in which further work needs to be carried out to understand the differences found. Many of the discordant items relate to the separate roles and associated issues of the two nurse groups.

Attitude of Health Personnel↗
PubMed2001

Foregut endoderm is required at head process stages for anteriormost neural patterning in chick.

Anterior definitive endoderm, the future pharynx and foregut lining, emerges from the anterior primitive streak and Hensen's node as a cell monolayer that replaces hypoblast during chick gastrulation. At early head process stages (4+ to 6; Hamburger and Hamilton) it lies beneath, lateral to and ahead of the ingressed axial mesoderm. Removal of the monolayer beneath and ahead of the node at stage 4 is followed by normal development, the removed cells being replaced by further ingressing cells from the node. However, similar removal during stages 4+ and 5 results in a permanent window denuded of definitive endoderm, beneath prechordal mesoderm and a variable sector of anterior notochord. The foregut tunnel then fails to form, heart development is confined to separated lateral regions, and the neural tube undergoes no ventral flexures at the normal positions in brain structure. Reduction in forebrain pattern is evident by the 12-somite stage, with most neuraxes lacking telencephalon and eyes, while forebrain expressions of the transcription factor genes GANF and BF1, and of FGF8, are absent or severely reduced. When the foregut endoderm removal is delayed until stage 6, later forebrain pattern appears once again complete, despite lack of foregut formation, of ventral flexure and of heart migration. Important gene expressions within axial mesoderm (chordin, Shh and BMP7) appear unaffected in all embryos, including those due to be pattern-deleted, during the hours following the operation when anterior brain pattern is believed to be determined. A specific system of neural anterior patterning signals, rather than an anterior sector of the initially neurally induced area, is lost following operation. Heterotopic lower layer replacement operations strongly suggest that these patterning signals are positionally specific to anteriormost presumptive foregut. The homeobox gene Hex and the chick Frizbee homologue Crescent are both expressed prominently within anterior definitive endoderm at the time when removal of this tissue results in forebrain defects, and the possible implications of this are discussed. The experiments also demonstrate how stomodeal ectoderm, the tissue that will, much later, form Rathke's pouch and the anterior pituitary, is independently specified by anteriormost lower layer signals at an early stage.

Animals↗
PubMed2001

Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain.

Rhombomeres are segmental units of the developing vertebrate hindbrain that underlie the reiterated organisation of cranial neural crest migration and neuronal differentiation. valentino (val), a zebrafish homologue of the mouse bzip transcription factor-encoding gene, kreisler, is required for segment boundary formation caudal to rhombomere 4 (r4). val is normally expressed in r5/6 and is required for cells to contribute to this region. In val(-) mutants, rX, a region one rhombomere in length and of mixed identity, lies between r4 and r7. While a number of genes involved in establishing rhombomeric identity are known, it is still largely unclear how segmental integrity is established and boundaries are formed. Members of the Eph family of receptor tyrosine kinases and their ligands, the ephrins, are candidates for functioning in rhombomere boundary formation. Indeed, expression of the receptor ephB4a coincides with val in r5/6, whilst ephrin-B2a, which encodes a ligand for EphB4a, is expressed in r4 and r7, complementary to the domain of val expression. Here we show that in val(-) embryos, ephB4a expression is downregulated and ephrin-B2a expression is upregulated between r4 and r7, indicating that Val is normally required to establish the mutually exclusive expression domains of these two genes. We show that juxtaposition of ephB4a-expressing cells and ephrin-B2a-expressing cells in the hindbrain leads to boundary formation. Loss of the normal spatial regulation of eph/ephrin expression in val mutants correlates not only with absence of boundaries but also with the inability of mutant cells to contribute to wild-type r5/6. Using a genetic mosaic approach, we show that spatially inappropriate Eph signalling underlies the repulsion of val(-) cells from r5/6. We propose that Val controls eph expression and that interactions between EphB4a and Ephrin-B2a mediate cell sorting and boundary formation in the segmenting caudal hindbrain.

Animals↗
PubMed2001

Implications of using high contrast mammography X-ray film-screen combinations.

The objective of this study was to determine the implications of using Fuji AD-M and Kodak min-R 2000, two high contrast X-ray film types developed for mammography. Evaluation of the Fuji AD-M film was divided into two parts. The first part was a contralateral comparison between mammograms using Fuji AD-M and Fuji UM-MA HC film-screen combinations. Fuji AD-M contrast was about 25% higher than that of Fuji UM-MA HC. The effect of increased contrast on image quality was investigated by visually grading the quality of information in different parts of each mammogram. Fuji AD-M film was generally judged to be better for overall diagnosis. However, 2.3% of mammograms produced using Fuji AD-M film were not acceptable and might have led to a technical recall of the patient. In the second part of this study, sets of mammograms from women attending mobile screening units were reviewed. One unit used Fuji AD-M film and the other used Kodak min-R 2000 film. Both samples of mammograms were digitized and analysed. The average film gradients between an optical density (OD) of 0.25 and 2.00 above base plus fog were 4.38 for Fuji AD-M film and 3.77 for Kodak min-R 2000 film. The main breast regions of the mammograms were judged to be satisfactorily displayed when breast tissues were above ODs of approximately 0.6 for Fuji AD-M film and 0.8 for Kodak min-R 2000 film.

Adult↗
PubMed2001

Laparoscopic ultrasound with radiofrequency ablation in cirrhotic patients with hepatocellular carcinoma: technique and technical considerations.

The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. CT-guided percutaneous radiofrequency ablation (RFA) has been shown to be efficacious in treatment of unresectable HCC. CT-guided RFA, however, may fail to detect small intrahepatic metastases and tumor thrombi, which thus minimizes possible gains from the procedure. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC metastases many of which were missed by CT. Combining intraoperative laparoscopic ultrasound with laparoscopic RFA greatly utilizes advances in both fields and is technically feasible. Our objective is to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RFA in treatment of HCC. Childs class B patients with unresectable HCC were considered for this study. Twelve patients underwent laparoscopic ultrasound and RFA of 17 lesions. Tumors ranged from 0.27 to 7 cm in diameter. Laparoscopic ultrasound identified tumor not detected preoperatively in one patient (8.3%). A single pneumothorax was the only complication. A single patient (8.3%) had recurrent disease and accounted for the only mortality in the study. We conclude that the use of both laparoscopic ultrasound and RFA is an excellent use of existing technology. The procedure combines improved tumor localization with the means to treat patients with unresectable disease. Because RFA is a relatively recent development long-term results are not yet available. Randomized prospective studies comparing RFA with other modalities will determine the ultimate utility of this procedure.

Adult↗
PubMed2000

Prescribing costs. Braking point.

A joint hospital, health authority and PCG initiative to improve prescribing has produced significant savings in the PCG involved. The venture included the appointment of a medicines management pharmacist to work with practices, and a survey to ascertain GPs' prescribing needs. GPs considered the most important issues to be developing local disease management guidelines, education and repeat prescribing. Guidelines on dyspepsia management have resulted in a 4.9 per cent reduction in the cost of prescribing gastrointestinal drugs. Antibiotic prescribing has also fallen.

Anti-Bacterial Agents↗
PubMed2000

FGF and genes encoding transcription factors in early limb specification.

SnR, twist and Fgf10 are expressed in presumptive limb territories of early chick embryos. When FGF-2/FGF-8 beads are implanted in chick flank, an ectopic limb develops and SnR is irreversibly activated as early as 1 h. Ectopic Fgf10 and twist expression are activated much later at 17 and 20 h, respectively. FGF-10 can also induce SnR, but much later, and in this case activation occurs simultaneously with that of twist and Fgf10 via the Fgf8- expressing ridge. Tbx-4 and Tbx-5 are expressed in leg and wing forming regions, respectively, in a similar pattern to SnR and twist. FGF-2 leads to ectopic expression of Tbx-4 and Tbx-5 as rapidly as ectopic expression of SnR, but the patterns of ectopic transcripts suggest that induction of SnR and Tbx gene expression occur via different pathways.

Animals↗
PubMed2000

Effects of a pharmacist's medication review in nursing homes. Randomised controlled trial.

BACKGROUND: Older people in nursing and residential homes often have complex disabilities and behavioural disturbances. Recent publicity has highlighted the dangers of medication in this group, and controls over prescribing have been suggested. AIMS: To investigate the effect of a review of medication by a pharmacist. METHOD: An 8-month prospective trial of an active medication review by a pharmacist was carried out on 330 residents in nursing homes in Manchester. RESULTS: The intervention group experienced greater deterioration in cognitive function and behavioural disturbance than the control group, but the changes in depression and quality of life were similar for both groups. The number of drugs prescribed fell in the intervention group, but not in the control group, with a corresponding saving in drug costs. The number of deaths was significantly smaller in the intervention homes during the intervention period (4 v. 14) but not overall during the study period as a whole (26 v. 28). CONCLUSION: This clinical intervention reduced the number of medicines prescribed to elderly people in nursing homes, with minimal impact on their morbidity and mortality.

Aged↗
PubMed2000

Skin edge perception in mammograms: a comparison of two film-screen combinations.

The entire skin edge is not always seen on mammograms. The importance of demonstrating the full extent of the breast on a mammogram is uncertain, but there are implications for optimizing film design and use. The new Agfa HDR film has been designed to improve visualization of the skin edge without compromising overall contrast. A quantitative and qualitative comparison between Agfa HDR and the Fuji UMMA film has been performed. A total of 216 mammograms from 54 symptomatic women were analysed. For each view on each woman, one breast was imaged using Fuji UMMA film and the other using Agfa HDR film. The target density achieved on quality control films of PMMA blocks was 1.70 +/- 0.10 for both film types. A radiologist graded the skin edges of all the films as visible, just visible or dark. Measurements were made of the optical densities in the skin edge region and on the fully exposed black part of the film, adjacent to the skin line. 70% of the HDR films had visible skin edges compared with 43% of the UMMA films. 2% of the HDR films had dark skin edges compared with 26% of the UMMA films. Optical densities at the skin edge were broadly similar for the two films and in the range 3.6 +/- 0.3. However, the density of the black part of the Agfa film was about 0.5 higher than with the Fuji film and it appears that this was the main reason the skin edge region was better visualized with the Agfa film.

Female↗
PubMed2000

Gene interference using antisense oligodeoxynucleotides on whole chick embryos. Optimal ring and roller-bottle culture technique.

Details are given of an advanced version of the ring method of chick embryo culture. This ensures good development from early blastoderm stages even when the culturing procedure is interrupted by the extended periods required for collecting matched embryo samples and for preparing antisense treatment. Antisense oligodeoxynucleotide treatment, in short-term incubation before return of blastoderms to their ring cultures, is then described. An alternative, roller-bottle, culture method for continued development after treatment is also described. Criteria for the validity and success of this gene interference method are given. While the text is meant to be of detailed practical help to those inexperienced in embryo culture, a preliminary reading, and familiarity with its sectional (Subheading) structure, is recommended before work is undertaken.

Animals↗
PubMed2000

Effects of follistatin and BMP4 proteins on early dorso-ventral patterning in chick.

In Xenopus and zebrafish certain bone morphognetic proteins (BMPs), and proteins that antagonise these by preventing their interaction with receptors, constitute a morphogen system in primary dorso-ventral patterning. This system may be directly involved in the parallel processes, within mesoderm and ectoderm, whereby the boundaries of the dorsal (paraxial) mesoderm and the neural plate are established. The bird blastoderm, amenable to grafting techniques and to direct exposure to specific proteins, has provided an opportunity to explore the phylogenetic conservation of such antagonistic system. We have grafted the gastrular organiser (node) into hosts, testing the effects of prior exposure of either grafted or host tissue to Follistatin (a known antagonist of TGFbeta superfamily ligands including BMP4) or to BMP4 protein. Strong, converse effects are seen from the two agents, the most consistent being on the sizes of new dorsalised areas (second neural plates) induced in host epiblast. Follistatin also enhances extension movements due to grafts, though without clear effect upon the rostro-caudal completeness of new patterns. Neural induction in chick epiblast by grafted mouse nodes are also more extensive, after their pre-incubation in Follistatin. Follistatin potentiates other, unknown but distinctive signals coming from the node, being unable to convert other non-inducing pieces of blastoderm into organisers on grafting. Pre-incubation of early blastoderms in BMP4 has such profound effects on normal dorsal axial development that host responsiveness of these blastoderms as hosts to node grafts is difficult to assess. Follistatin has no such overt effect on host development, but greatly enhances the competence of host epiblast to grafts of untreated nodes. Early chick BMP4 and BMP7 expressions are consistent with the proposed roles, though Follistatin is probably an experimental tool only in the present study.

Animals↗
PubMed1999

Flik, a chick follistatin-related gene, functions in gastrular dorsalisation/neural induction and in subsequent maintenance of midline Sonic hedgehog signalling.

We have targetted the chick gene Flik with antisense oligodeoxynucleotide treatment at gastrular stages, when it is expressed in organiser-derived structures of the midline (K. Patel et al., 1996, Dev. Biol. 178, 327-342). A specific syndrome of deficient axial patterning and holoprosencephaly is produced. Most aspects of this syndrome can be understood as due to attenuation of dorsalising and neural-inducing signals during gastrulation, followed by failure to maintain the later signals from chordamesoderm/neural midline that pattern the mesodermal and neural cross sections during subsequent stages. Anatomical effects are first apparent at early neurula stages and correspond with what might be expected from a reduced counteraction of the ventralising Bone morphogenetic protein (BMP) pathway at the earlier stages, coupled with inadequate Sonic hedgehog (Shh) signalling subsequently. Delay in the clearing of BMP-4 RNA expression from the presumptive neural region at gastrulation is indeed seen, though chordin RNA expression within organiser derivatives remains normal. Subsequently, specific attenuation of chordamesoderm and neural midline Shh expression is observed. Brief preincubation of stage 4 chick blastoderms in supernatant from Xenopus oocytes that have been injected with Flik RNA prolongs and enhances the competence of their peripheral epiblast to respond to neural inductive signals from grafted Hensen's nodes. This effect specifically mimics that recently observed using microg/ml solutions of recombinant Follistatin (D. J. Connolly et al., 1999, Int. J. Dev. Biol., in press), further suggesting that Flik protein might act in vivo by somehow modulating activity of signalling pathways through BMP or other TGFbeta-related ligands. We discuss the significance of the observations in relation to recent ideas about neural induction, about possible redundancy in gene action, and about subsequent patterning of the axial cross section, suggesting that a Flik function in autocrine/paracrine maintenance of later midline Shh signalling represents a role of the gene separate from that in primary dorsalisation/neural induction.

Amino Acid Sequence↗
PubMed1999

Nodal signalling and the roles of the transcription factors SnR and Pitx2 in vertebrate left-right asymmetry.

Left-specific mesodermal expression of the homeobox gene Pitx2 links a gastrula-stage intercellular signalling cascade to the later development of vertebrate left-right organ asymmetry through the Nodal signalling pathway [1] [2][3] [4][5] [6]. SnR (Drosophila snail-related), a gene conserved in vertebrates and encoding a zinc-finger protein, appears to function in a similar manner to Pitx2, but through right-specific mesodermal expression [7] [8]. Here, we present direct evidence for an earlier proposal [7] that Nodal signalling specifically represses expression of SnR in left lateral mesoderm, and thus ensures its normal confinement to the right, while activating Pitx2 on the left. We addressed the relationship between Pitx2 and SnR using antisense disruption of SnR. Relatively severe antisense-SnR treatment led to massive ectopic expression of Pitx2 on the right, accompanied by randomisation of situs with embryos showing aspects of left-cardiac isomerism. This indicates a gene cascade relationship in the propagation of left-right information, whereby nodal activates Pitx2 on the left through a double-negative mechanism involving the repression of SnR's repressor role on Pitx2. Milder antisense-SnR treatment reversed heart-loop direction and embryo torsion at significant incidence, although Pitx2 expression remained normally left-confined throughout. This reversed morphology following SnR disruption alone appeared different from that in which additional ectopic right-hand Pitx2 expression was seen. Therefore, in addition to their regulatory gene cascade relationship, these two transcription factors appear to have further, parallel but non-redundant, roles in directly controlling normally right- and left-specific morphogenetic processes.

Animals↗
PubMed1999

The significance of spontaneous resolution of breast calcification.

Spontaneously resolving breast microcalcification is a rarely reported occurrence. A retrospective review was carried out on 33 cases of resolving benign and indeterminate microcalcification identified from 108,000 screening mammograms from the South West London Breast Screening Service. Four further cases are reported from The Jarvis Breast Screening Centre. No interval cancers were identified in women with microcalcification which initially showed benign appearances. However, 36.4% of the group with resolving indeterminate microcalcification subsequently developed cancers. It is recommended that this change should prompt full investigation and close follow-up or excision. While the majority of spontaneously resolving microcalcification is associated with benign processes, it is concluded that a significant proportion of disappearing indeterminate microcalcification is associated with malignancy.

Aged↗
PubMed1999

Analysis of optical density and contrast in mammograms.

The objective of this project is the development of tools for the UK NHSBSP to assess image quality quantitatively in clinical films, for the purposes of optimizing imaging procedures and audit. As an initial step, 120 mammograms of 46 women on a single day of screening were digitized and analysed to produce indices of optical density (OD) and contrast. Analysis was performed on three regions of interest (ROI): pectoral muscle, main breast and skin edge. Two radiologists independently graded the quality of information in the different parts of each mammogram, and categorized breast type as either "dense", "mixed density" or "fatty". Measurements of contrast and OD generally correlated well with the opinions of the radiologists. For the oblique mammograms, the mean OD in the main breast ranged between films from 1.25 to 2.24 with a mean of 1.69 +/- 0.02. In the craniocaudal mammograms, the mean OD in the main breast ROI ranged from 1.14 to 1.94 with a mean of 1.61 +/- 0.05. The OD for a quality control film of a 40 mm block of PMMA exposed on the same day with this system was 1.53. A contrast index (CI) was calculated for each mammogram as the difference between the points of maximum and minimum OD in the main breast. Mean CI was 1.02 +/- 0.09 for fatty breasts, 1.50 +/- 0.10 for mixed density breasts and 2.05 +/- 0.23 for dense breasts. A review of the radiologist assessments indicated that the main breast was satisfactorily displayed when glandular and fatty tissues were displayed within the OD range 0.8-2.9. An analysis of the dynamic range requirements showed that 17% of films had a dynamic range that lay above that calculated using the suggested OD limits.

Breast Neoplasms↗